Submissions for variant NM_201253.3(CRB1):c.4205T>C (p.Met1402Thr)

dbSNP: rs767920858

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001099415	SCV001255870	uncertain significance	Retinitis pigmentosa	2017-04-28	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV001099416	SCV001255871	uncertain significance	Pigmented paravenous retinochoroidal atrophy	2017-04-28	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV001099417	SCV001255872	uncertain significance	Leber congenital amaurosis 8	2017-04-28	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001873487	SCV002315724	uncertain significance	Retinitis pigmentosa 12; Leber congenital amaurosis 8	2022-07-06	criteria provided, single submitter	clinical testing	In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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) performed at Invitae indicates that this missense variant is not expected to disrupt CRB1 protein function. ClinVar contains an entry for this variant (Variation ID: 875506). This variant has not been reported in the literature in individuals affected with CRB1-related conditions. This variant is present in population databases (rs767920858, gnomAD 0.0009%). This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1402 of the CRB1 protein (p.Met1402Thr).
Genome-Nilou Lab	RCV001099417	SCV004180926	uncertain significance	Leber congenital amaurosis 8	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001099416	SCV004180927	uncertain significance	Pigmented paravenous retinochoroidal atrophy	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003449552	SCV004180928	uncertain significance	Retinitis pigmentosa 12	2023-04-11	criteria provided, single submitter	clinical testing