Submissions for variant NM_019098.4(CNGB3):c.1208G>A (rs147876778)

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics	RCV000435881	SCV000225390	likely benign	not specified	2015-04-22	criteria provided, single submitter	clinical testing
GeneDx	RCV000435881	SCV000512655	likely benign	not specified	2016-11-09	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Genomic Research Center,Shahid Beheshti University of Medical Sciences	RCV000501136	SCV000588362	pathogenic	Abnormality of the eye	2017-06-18	criteria provided, single submitter	clinical testing
Molecular Genetics Laboratory,Institute for Ophthalmic Research	RCV000597492	SCV000700212	pathogenic	Achromatopsia	2018-03-20	criteria provided, single submitter	research
Invitae	RCV000132679	SCV001105918	benign	not provided	2020-12-05	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV001164460	SCV001326587	likely benign	Stargardt disease 1	2017-04-27	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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Broad Institute Rare Disease Group, Broad Institute	RCV001164460	SCV001435146	likely benign	Stargardt disease 1		criteria provided, single submitter	research	The p.Arg403Gln variant in CNGB3 has been identified in 3 homozygous Pakistani individuals with progressive cone dystrophy, 1 homozygous Pakistani individual with complete achromatopsia, and in the heterozygous state in 1 individual with progressive cone dystrophy, segregated with eye disease in 4 relatives from 1 family (PMID: 15161866, 24504161), and has been identified in >2% of South Asian chromosomes and 13 homozygotes by ExAC (http://gnomad.broadinstitute.org/). In vitro functional studies provide some evidence that the p.Arg403Gln variant may slightly impact protein function (PMID: 16379026). However, these types of assays may not accurately represent biological function. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely benign for autosomal recessive progressive cone dystrophy.
Nilou-Genome Lab	RCV000174144	SCV001737262	likely benign	Achromatopsia 3	2021-05-18	criteria provided, single submitter	clinical testing
Department of Ophthalmology and Visual Sciences Kyoto University	RCV000132679	SCV000172631	probable-non-pathogenic	not provided		no assertion criteria provided	not provided	Converted during submission to Likely benign.
Molecular Genetics Laboratory,Institute for Ophthalmic Research	RCV000174144	SCV000575809	likely pathogenic	Achromatopsia 3	2017-03-27	no assertion criteria provided	research
Human Genetics - Radboudumc,Radboudumc	RCV000678546	SCV000804624	uncertain significance	Retinitis pigmentosa	2016-09-01	no assertion criteria provided	clinical testing
Sharon lab,Hadassah-Hebrew University Medical Center	RCV000597492	SCV001161027	pathogenic	Achromatopsia	2019-06-23	no assertion criteria provided	research
Natera, Inc.	RCV000597492	SCV001455000	uncertain significance	Achromatopsia	2020-01-08	no assertion criteria provided	clinical testing