Individual #00413224

ID_report	p1
Reference	PubMed: Wawrocka 2017
Remarks	Polish family, consanguineous; third cousin parents
Gender	M
Consanguinity	yes
Country	Poland
Population	Polish
Age at death	-
VIP	-
Data_av	-
Treatment	-
Panel size	1
Diseases	retinal disease
Owner name	LOVD
Database submission license
Created by	Anna Tracewska
Date created	2022-07-12 15:08:53 +02:00 (CEST)
Date last edited	N/A

Phenotypes

retinal disease (-)

Add phenotype for this disease

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Phenotype details: additional information on the phenotype of the individual, preferably use HPO terms only (http://www.human-phenotype-ontology.org/)

Diagnosis/Initial: initial diagnosis, before molecular testing

Diagnosis/Definite: phenotype individual after molecular testing (OMIM abbreviation)

Inheritance: Indicates the inheritance of the phenotype in the family; unknown, familial (autosomal/X-linked, dominant/ recessive), paternal (Y-linked), maternal (mitochondrial), isolated (sporadic) or complex
All options:

Unknown
Familial
Familial, autosomal dominant
Familial, autosomal recessive
Familial, X-linked
Familial, X-linked dominant
Familial, X-linked dominant, male sparing
Familial, X-linked recessive
Paternal, Y-linked
Maternal, mitochondrial
Isolated (sporadic)
Di-genic
Complex
- = Not applicable

Age/Examination: age at which the individual was examined.

35y = 35 years
04y08m = 4 years and 8 months
00y00m01d12h = 1 day and 12 hours
18y? = around 18 years
30y-40y = between 30 and 40 years
>54y = older than 54
? = unknown

Age/Diagnosis: age diagnosis was confirmed

35y = 35 years
04y08m = 4 years and 8 months
00y00m01d12h = 1 day and 12 hours
18y? = around 18 years
30y-40y = between 30 and 40 years
>54y = older than 54
? = unknown

Age/Onset: Age first symptoms disease appeared in individual:

35y = 35 years
04y08m = 4 years and 8 months
00y00m01d12h = 1 day and 12 hours
18y? = around 18 years
30y-40y = between 30 and 40 years
>54y = older than 54
? = unknown

Phenotype/Onset: individual's phenotype at Age/Onset described using HPO

Protein: result from protein staining

How to query this table

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Operator	Column type	Example	Matches
	Text	Arg	all entries containing 'Arg'
space	Text	Arg Ser	all entries containing 'Arg' and 'Ser'
\|	Text	Arg\|Ser	all entries containing 'Arg' or 'Ser'
!	Text	!fs	all entries not containing 'fs'
^	Text	^p.(Arg	all entries beginning with 'p.(Arg'
$	Text	Ser)$	all entries ending with 'Ser)'
=""	Text	=""	all entries with this field empty
=""	Text	="p.0"	all entries exactly matching 'p.0'
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!=""	Text	!="p.0"	all entries not exactly matching 'p.0?'
combination	Text	*\|Ter !fs	all entries containing '*' or 'Ter' but not containing 'fs'
	Date	2020	all entries matching the year 2020
\|	Date	2020-03\|2020-04	all entries matching March or April, 2020
!	Date	!2020-03	all entries not matching March, 2020
<	Date	<2020	all entries before the year 2020
<=	Date	<=2020-06	all entries in or before June, 2020
>	Date	>2020-06	all entries after June, 2020
>=	Date	>=2020-06-15	all entries on or after June 15th, 2020
combination	Date	2019\|2020 <2020-03	all entries in 2019 or 2020, and before March, 2020
	Numeric	23	all entries exactly matching 23
\|	Numeric	23\|24	all entries exactly matching 23 or 24
!	Numeric	!23	all entries not exactly matching 23
<	Numeric	<23	all entries lower than 23
<=	Numeric	<=23	all entries lower than, or equal to, 23
>	Numeric	>23	all entries higher than 23
>=	Numeric	>=23	all entries higher than, or equal to, 23
combination	Numeric	>=20 <30 !23	all entries with values from 20 to 29, but not equal to 23

Some more advanced examples:

Example	Matches
Asian	all entries containing 'Asian', 'asian', including 'Caucasian', 'caucasian', etc.
Asian !Caucasian	all entries containing 'Asian' but not containing 'Caucasian'
Asian\|African !Caucasian	all entries containing 'Asian' or 'African', but not containing 'Caucasian'
"South Asian"	all entries containing 'South Asian', but not containing 'South East Asian'

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Phenotype ID	Phenotype details	Diagnosis/Initial	Diagnosis/Definite	Inheritance	Age/Examination	Age/Diagnosis	Age/Onset	Phenotype/Onset	Protein	Owner
0000305205	5-6y: presented with low visual acuity (0.05-0.1), hypermetropic astigmatism (of 2.5-3.0 cyl D), total inability to distinguish colors, and visual field constriction; fundi: pale optic discs and round, dystrophic changes in the central maculae with pigment rearrangements; visual acuity gradually decreased to counting fingers from 1.5 m - 20y, and hand movements - 25y; >20y: extensive retinochoroidal atrophy of both maculae, narrowing of the retinal vessels, secondary optic nerve atrophy, and pigment deposits in the peripheral retina; bilateral posterior subcapsular cataracts; night vision getting worse, but still better than in bright light; concentric narrowing of the visual fields (7-10deg); optical coherence tomography: flat foveae profile, photoreceptor atrophy, disturbed retinal layer structure; flash electroretinogram: totally extinguished photopic and scotopic responses, multifocal electroretinogram: no central maculae responses; ocular ultrasound: optic disc drusen and vitreous focal condensations; tooth enamel hypoplasia in early childhood; lost their permanent teeth shortly after 20y; apparent muscular overgrowth of the legs not observed in the other family members; neurological examination: patient denied muscular weakness, cramps, myalgia, gait difficulties, rigidity, sensation abnormalities, fasciculations, respiratory problems, hearing impairment, dysphagia, or tendency to fall; continued to work as a professional physiotherapist; nystagmus, mild contractures of the knees and Achilles tendons, weakened deep tendon reflexes from biceps and brachioradialis, symmetric overgrowth of the legs, particularly in the quadriceps and calves, weak patellar Achilles tendon reflexes, and impaired heel walking due to Achilles tendon contractures; the rest of the neurological examination normal; increased creatine kinase concentration in blood (1,051 U/L, normal 38-174 U/L), mild elevation of transaminases (ALT 58 IU/L, normal 10-41 U/L; AST 44 IU/L,normal10-37IU/L), lactic acid and LDH: normal; motor and sensory nerve conduction velocities: normal; evoked compound motor action potentials and sensory nerve action potentials: normal; needle electromyography of the right deltoid, tibialis anterior, and vastus lateralis muscles: increased recruitment pattern, with spontaneous activity demonstrated as pseudomyotonic discharges; motor unit action potentials duration of all the muscles shortened, while amplitudes remained normal - the electromyographic examination demonstrated myopathic involvement	-	Jalili Syndrome	Familial, autosomal recessive	30y	-	0m	congenital nystagmus, photophobia appeared later in infancy	-	LOVD

Screenings

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Template: Template(s) used to detect the sequence variant; DNA (genomic DNA), RNA (cDNA) or protein
All options:

DNA
RNA = RNA (cDNA)
protein
? = unknown

Technique: technique(s) used to identify the sequence variant.
All options:

? = unknown
ARMS = amplification refractory mutation system
arrayCGH = array for Comparative Genomic Hybridisation
arrayMET = array for methylation analysis
arraySEQ = array for resequencing
arraySNP = array for SNP typing
arrayCNV = array for Copy Number Variation (SNP and CNV probes)
ASO = allele-specific oligo hybridisation
BESS = Base Excision Sequence Scanning
CMC = Chemical Mismatch Cleavage
COBRA = Combined Bisulfite Restriction Analysis
CSCE = Conformation Sensitive Capillary Electrophoresis
CSGE = Conformation Sensitive Gel Electrophoresis
ddF = dideoxy Fingerprinting
DGGE = Denaturing-Gradient Gel-Electrophoresis
DHPLC = Denaturing High-Performance Liquid Chromatography
DOVAM = Detection Of Virtually All Mutations (SSCA variant)
DSCA = Double-Strand DNA Conformation Analysis
DSDI = Detection Small Deletions and Insertions
EMC = Enzymatic Mismatch Cleavage
expr = expression analysis
FISH = Fluorescent In-Situ Hybridisation
FISHf = fiberFISH
HD = HeteroDuplex analysis
HPLC = High-Performance Liquid Chromatography
IEF = IsoElectric Focussing
IHC = Immuno-Histo-Chemistry
Invader = Invader assay
MAPH = Multiplex Amplifiable Probe Hybridisation
MAQ = Multiplex Amplicon Quantification
MCA = Melting Curve Analysis, high-resolution (HRMA)
microscope = microscopic analysis (karyotype)
microsat = microsatellite genotyping
minigene = expression minigene construct
MIP = Molecular Inversion Probe amplification
MIPsm = single molecule Molecular Inversion Probe amplification
MLPA = Multiplex Ligation-dependent Probe Amplification
MLPA-ms = Multiplex Ligation-dependent Probe Amplification, methylation specific
MS = mass spectrometry
Northern = Northern blotting
NUC = nuclease digestion (RNAseT1, S1)
OM = optical mapping
PAGE = Poly-Acrylamide Gel-Electrophoresis
PCR = Polymerase Chain Reaction
PCRdd = PCR, digital droplet
PCRdig = PCR + restriction enzyme digestion
PCRh = PCR, haloplex
PCRlr = PCR, long-range
PCRm = PCR, multiplex
PCRms = PCR, methylation sensitive
PCRq = PCR, quantitative (qPCR)
PCRrp = PCR, repeat-primed (RP-PCR)
PCRsqd = PCR, semi-quantitative duplex
PE = primer extension (APEX, SNaPshot)
PEms = primer extension, methylation-sensitive single-nucleotide
PFGE = Pulsed-Field Gel-Electrophoresis (+Southern)
PTT = Protein Truncation Test
RFLP = Restriction Fragment Length Polymorphisms
RT-PCR = Reverse Transcription and PCR
RT-PCRq = Reverse Transcription and PCR, quantitative
SBE = Single Base Extension
SEQ = SEQuencing (Sanger)
SEQb = bisulfite SEQuencing
SEQp = pyroSequencing
SEQms = sequencing, methylation specific
SEQ-ON = next-generation sequencing - Oxford Nanopore
SEQ-NG = next-generation sequencing
SEQ-NG-RNA = next-generation sequencing RNA
SEQ-NG-H = next-generation sequencing - Helicos
SEQ-NG-I = next-generation sequencing - Illumina/Solexa
SEQ-NG-IT = next-generation sequencing - Ion Torrent
SEQ-NG-R = next-generation sequencing - Roche/454
SEQ-NG-S = next-generation sequencing - SOLiD
SEQ-PB = next-generation sequencing - Pacific Biosciences
SNPlex = SNPlex
Southern = Southern blotting
SSCA = Single-Strand DNA Conformation polymorphism Analysis (SSCP)
SSCAf = fluorescent SSCA (SSCP)
STR = Short Tandem Repeat
TaqMan = TaqMan assay
Western = Western blotting
- = not applicable

Tissue: tissue type used for analysis

Remarks: remarks regarding the screening like WGS (whole genome sequencing), WES (whole exome sequencing, gene panel (incl. a list of genes analysed), etc.

Screening ID	Template	Technique	Tissue	Remarks	Genes screened	Variants found	Owner
0000414495	DNA	SEQ-NG;SEQ	blood	exome sequencing	CNNM4	1	LOVD

Variants

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Allele: On which allele is the variant located? Does not necessarily imply inheritance! 'Paternal' (confirmed or inferred), 'Maternal' (confirmed or inferred), 'Parent #1' or #2 for compound heterozygosity without having screened the parents, 'Unknown' for heterozygosity without having screened the parents, 'Both' for homozygozity.

Effect: The variant's effect on the function of the gene/protein, displayed in the format 'R/C'. R is the value reported by the source (publication, submitter) and this classification may vary between records. C is the value concluded by the curator. Note that in some database the curator uses Summary records to give details on the classification of the variant.Values used: '+' indicating the variant affects function, '+?' probably affects function, '-' does not affect function, '-?' probably does not affect function, '?' effect unknown, '.' effect was not classified.

Classification method: The method used for the clinical classification of this variant.
All options:

ACMG
ACGS
EAHAD-CFDB
ENIGMA
IARC
InSiGHT
kConFab
other

Clinical classification: Clinical classification of variant, preferably based on standardised criteria (e.g. ACMG), directed on the clinical consequences as published/submitted, indicated using an enriched system including inheritance: e.g. pathogenic, pathogenic (dominant), pathogenic (recessive), pathogenic (!), pathogenic (maternal), pathogenic (paternal). Standard inheritance is covered by dominant/recessive, imprinting by maternal/paternal. A '!' warns for exceptional circumstances to be explained in the 'Remarks' field (low penetrance, variants pathogenic in heterozygous state only, hypomorphic/hypermorphic variants, protective variants, etc.). Non-disease consequences (e.g. drug metabolism (pharmacogenetics), risk factor, blood group, tasting bitter) are indicated using additions to the benign classification; benign (dominant), benign (recessive), benign (!), etc. The value 'association' is used for variants associated with a phenotype and 'NA' for variants from in vitro/in silico records. NOTE: classification may differ from the opinion of the curator as given in a variant SUMMARY-record or the 'Functional effect concluded'). NOTE: pathogenic/likely pathogenic should go together with "variant (probably) affects function" In ClassFunctional.
All options:

pathogenic
pathogenic (dominant)
pathogenic (recessive)
pathogenic (!)
pathogenic (maternal)
pathogenic (paternal)
likely pathogenic
likely pathogenic (dominant)
likely pathogenic (recessive)
likely pathogenic (!)
likely pathogenic (maternal)
likely pathogenic (paternal)
VUS
VUS (!)
likely benign
likely benign (dominant)
likely benign (recessive)
likely benign (!)
likely benign (maternal)
likely benign (paternal)
benign
benign (dominant)
benign (recessive)
benign (!)
benign (maternal)
benign (paternal)
conflicting
association
NA

DNA change (genomic) (hg19): HGVS description of variant at DNA level, based on the genomic (chromosomal) DNA reference sequence; e.g. g.12345678C>T, g.12345679del, g.12345678_12345890dup

DNA change (hg38): HGVS description of variant at DNA level, based on the hg38 genomic (chromosomal) eference sequence; e.g. g.12345678C>T, g.12345679del, g.12345678_12345890dup

Published as: listed only when different from "DNA change"; variant as reported originally (e.g. 521delT). Variants seen in animal models, tested in vitro, predicted from RNA analysis, etc. are described between brackets like c.(456C>G)

ISCN: description of the variant according to ISCN nomenclature

DB-ID: database ID of variant, grouping multiple observations of the same variant together, starting with the HGNC gene symbol, followed by an underscore (_) and a six digit number (e.g. DMD_012345). _000000 is used for variants where DNA was not analysed (change predicted from RNA analysis), variants seen in animal models or variants not seen in humans but functionally tested in vitro

Variant remarks: remarks regarding variant described, e.g. germline mosaicism in mother, 345 kb deletion, muscle RNA analysed, not in 200 control chromosomes tested, on founder haplotype, etc.

Reference: publication describing the variant submitted, incl. links to OMIM, PubMed or other source, e.g. "den Dunnen ASHG2003 P2346"

ClinVar ID: ID of variant in ClinVar database

dbSNP ID: the dbSNP ID

Origin: Origin of variant/record: Germline = in all cells, De novo = in all cells, but not in either parent, Germline/De novo (untested) = in all cells, parents not tested (use only when De novo is likely, e.g. isolated/sporadic cases with dominant disease), Somatic = present in a subset of cells, but not in either parent, Uniparental disomy = from parental disomy (maternal or paternal), CLASSIFICATION record = submitter only sharing variant classification (note another report may share Individual data), SUMMARY record = master summary record from curator (may link to another database), In vitro (cloned) = data resulting from in vitro functional assays, animal model = data from animal model, Artefact = false positive variant call, DUPLICATE record = variant already described on another chromosome (e.g. unbalanced translocation, duplicating transposition, 2nd fusion transcript, etc.)
All options:

Germline
De novo
Germline/De novo (untested)
Somatic
Uniparental disomy
Uniparental disomy, maternal allele
Uniparental disomy, paternal allele
CLASSIFICATION record
SUMMARY record
In vitro (cloned)
In silico
animal model
Artefact
DUPLICATE record
Unknown
Not applicable

Segregation: Indicates whether the variant segregates with the phenotype (yes), does not segregate with the phenotype (no) or segregation is unknown (?)
All options:

? = unknown
yes = segregates with phenotype
no = does not segregate with phenotype
- = not applicable

Frequency: frequency in which the variant was found; e.g 5/760 chromosomes (in 5 of 760 chromosomes tested), 1/33 patients (in 1 of 33 patients analysed in study), 0.05 controls (in 5% of control cases tested)

Re-site: restriction enzyme recognition site created (+) or destroyed (-); e.g. BglII+;BamHI-

VIP: variant VIP-status was requested for matchmaking - need collaboration(s) to crack the case - please contact the submitter/curator. NOTE: to get VIP status ask the curator.

Methylation: result of methylation test; GOM (gain of methylation), LOM (loss of methylation), 30% (30% methylated). NOTE: when several tests were done mention the method as well (e.g. MS-PCR 75%)

IDbase Accession Number: IDbase Accession Number

VariO/DNA: variation ontology annotation at DNA level
All options:

DNA substitution (VariO:0136)
transition (VariO:0313)
pyrimidine transition (VariO:0314)
purine transition (VariO:0315)
not changed (VariO:0140)
DNA deletion (VariO:0141)
DNA insertion (VariO:0142)
DNA indel (VariO:0143)
DNA inversion (VariO:0145)
DNA translocation (VariO:0144)
transversion (VariO:0316)

VariO/Protein: variation ontology annotation at protein level
All options:

protein truncation (VariO:0015)
sequence retaining amino acid deletion (VariO:0016)
nonsynonymous variation (VariO:0017)
amino acid insertion (VariO:0018)
amphigoric amino acid insertion (VariO:0019)
sequence retaining amino acid insertion (VariO:0020)
amino acid substitution (VariO:0021)
amino acid indel (VariO:0022)
amphigoric amino acid indel (VariO:0023)
missing protein (VariO:0240)
sequence retaining amino acid indel (VariO:0029)
alternatively initiated protein (VariO:0443)
artificial protein variation (VariO:0246)
mistranslated protein (VariO:0330)
protein structural inheritance (VariO:0026)
epigenetic protein variation (VariO:0025)
post translational modification (VariO:0028)
proteinaceous infection (VariO:0027)

VariO/RNA: variation ontology annotation at RNA level
All options:

RNA substitution (VariO:0312)
transition (VariO:0313)
pyrimidine transition (VariO:0314)
purine transition (VariO:0315)
transversion (VariO:0316)
missense variation (VariO:0308)
initiation codon change (VariO:0317)
termination codon change (VariO:0309)
nonsense variation (VariO:0310)
silent variation (VariO:0318)
RNA deletion (VariO:0319)
in-frame deletion (VariO:0320)
out-of-frame deletion (VariO:0321)
RNA insertion (VariO:0326)
in-frame insertion (VariO:0332)
out-of-frame insertion (VariO:0327)
RNA indel (VariO:0311)
in-frame indel (VariO:0030)
out-of-frame indel (VariO:0031)
effect on RNA splicing (VariO:0362)
intron gain (VariO:0364)
RNA splicing change (VariO:0334)
exon loss (VariO:0381)
missing RNA (VariO:0245)
unsense variation (VariO:0514)

Exon: number of exon/intron containing variant; 2 = exon 2, 12i = intron 12, 2i_7i = from intron 2 to intron 7, 8i_9 = intron 8/exon 9 boundary, _1 = 5' to exon 1, 18_ = 3' of exon 18, _1_18_ = encompassing the entire 18-exon gene

DNA change (cDNA): description of variant at DNA level, based on a coding DNA reference sequence (following HGVS recommendations); e.g. c.123C>T, c.123_145del, c.123_126dup. For deletions/duplications extending beyond the reference transcript resp. {0}/{2} is used to replace del/dup. Extent of the deletion/duplication should be specified using the genomic description (g.). "-" indicates the variant described on genomic level does not affect the coding DNA reference sequence.

Haplotype: haplotype on which variant was found

RNA change: description of variant at RNA level (following HGVS recommendations).

r.123c>u
r.? = unknown
r.(?) = RNA not analysed but probably transcribed copy of DNA variant
r.spl? = RNA not analysed but variant probably affects splicing
r.(spl?) = RNA not analysed but variant may affect splicing
r.0? = change expected to abolish transcription

Protein: description of variant at protein level (following HGVS recommendations).

p.(Arg345Pro) = change predicted from DNA (RNA not analysed)
p.Arg345Pro = change derived from RNA analysis
p.? = unknown effect
p.0? = probably no protein produced

P-domain: region/domain protein affected

Exon_old: exon number according to older numbering

Predicted: predicted consequence of variant (RNA/protein level)
All options:

missense
nonsense
frameshift
no-stop
silent
splicing affected
splicing affected, exon skipped
splicing affected?
deletion
deletion, small
deletion, large
deletion, exon
deletion, multi exon
duplication
duplication, small
duplication, large
insertion
insertion, small
insertion, large
delins = insertion/deletion
conversion
other/complex

Type/DNA: type of variant at DNA level. NOTE: can be derived automatically from the variant description (for all levels)
All options:

substitution
deletion
deletion, small
deletion, large
duplication
duplication, small
duplication, large
insertion
insertion, small
insertion, large
delins = insertion/deletion
inversion
conversion
transposition
translocation
other/complex

Enzyme activity: activity variant enzym

mRNA level: Level of transcribed mRNA present in peripheral blood mononuclear cells. The level is indicated in relative terms as normal/(much) increased/(much) reduced/absent.

Predict-BioInf: predicted effect of variant using bioinformatic analysis tools (e.g. AGVGD, CADD, conservation, Grantham, MutationTaster, PolyPhen, REVEL, SIFT, splicing, etc.)

Legacy protein change: description of variant at protein level using a traditional (legacy) numbering system.

Protein level: Level of translated protein in peripheral blood mononuclear cells. The level is indicated in relative terms as normal/(much) increased/(much) reduced/absent.

1 entry on 1 page. Showing entry 1.

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How to query

Chr	Allele	Effect	Classification method	Clinical classification	DNA change (genomic) (hg19)	DNA change (hg38)	Published as	ISCN	DB-ID	Variant remarks	Reference	ClinVar ID	dbSNP ID	Origin	Segregation	Frequency	Re-site	VIP	Methylation	Owner	Gene	IDbase Accession Number	VariO/DNA	VariO/Protein	VariO/RNA	Exon	DNA change (cDNA)	Haplotype	RNA change	Protein	P-domain	Exon_old	Predicted	Type/DNA	Enzyme activity	mRNA level	Predict-BioInf	Legacy protein change	Protein level
2	Both (homozygous)	+?/.	-	likely pathogenic (recessive)	g.97427812T>C	g.96762075T>C	CNNM4 c.1076T>C, p.(Leu359Pro)	-	CNNM4_000053	homozygous	PubMed: Wawrocka 2017	-	-	Germline	yes	-	-	-	-	LOVD	CNNM4	-	-	-	-	4	NM_020184.3:c.1076T>C	-	r.(?)	p.(Leu359Pro)	-	-	-	-	-	-	-	-	-

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