NM_000266.4(NDP):c.370C>T (p.Leu124Phe) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 27, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001851794.4

Allele description [Variation Report for NM_000266.4(NDP):c.370C>T (p.Leu124Phe)]

NM_000266.4(NDP):c.370C>T (p.Leu124Phe)

Genes:

NDP-AS1:NDP antisense RNA 1 [Gene - HGNC]
NDP:norrin cystine knot growth factor NDP [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xp11.3

Genomic location:

Preferred name:

NM_000266.4(NDP):c.370C>T (p.Leu124Phe)

HGVS:

NC_000023.11:g.43949831G>A
NG_009832.1:g.28845C>T
NM_000266.4:c.370C>TMANE SELECT
NP_000257.1:p.Leu124Phe
NC_000023.10:g.43809077G>A
NR_046631.1:n.100G>A
Q00604:p.Leu124Phe

Protein change:

L124F; LEU124PHE

Links:

UniProtKB: Q00604#VAR_005505; OMIM: 300658.0006; dbSNP: rs28933684

NCBI 1000 Genomes Browser:

rs28933684

Molecular consequence:

NM_000266.4:c.370C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_046631.1:n.100G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002245653	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 27, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 8252044, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002245653

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 27, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A mutation in the Norrie disease gene (NDP) associated with X-linked familial exudative vitreoretinopathy.

Chen ZY, Battinelli EM, Fielder A, Bundey S, Sims K, Breakefield XO, Craig IW.

Nat Genet. 1993 Oct;5(2):180-3.

PubMed [citation]

PMID:: 8252044

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002245653.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on NDP protein function. ClinVar contains an entry for this variant (Variation ID: 10684). This missense change has been observed in individual(s) with familial exudative vitreoretinopathy (PMID: 8252044). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 124 of the NDP protein (p.Leu124Phe).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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