Submissions for variant NM_001142800.2(EYS):c.2000G>A (p.Arg667His)

dbSNP: rs549456693

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Center for Human Genetics Tuebingen	RCV000513214	SCV000609217	uncertain significance	not provided	2024-01-01	criteria provided, single submitter	clinical testing	EYS: PM2, BP4
Counsyl	RCV000670182	SCV000795009	uncertain significance	Retinitis pigmentosa 25	2017-10-24	criteria provided, single submitter	clinical testing
Invitae	RCV000513214	SCV001204999	uncertain significance	not provided	2022-09-27	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 667 of the EYS protein (p.Arg667His). This variant is present in population databases (rs549456693, gnomAD 0.2%). This missense change has been observed in individual(s) with retinitis pigmentosa (PMID: 28041643, 30718709, 31054281). ClinVar contains an entry for this variant (Variation ID: 438193). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.
Blueprint Genetics	RCV001074081	SCV001239650	uncertain significance	Retinal dystrophy	2018-12-15	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000504709	SCV001321746	uncertain significance	Retinitis pigmentosa	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Fulgent Genetics, Fulgent Genetics	RCV000670182	SCV002793255	uncertain significance	Retinitis pigmentosa 25	2022-05-26	criteria provided, single submitter	clinical testing
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000504709	SCV000599147	likely pathogenic	Retinitis pigmentosa	2015-01-01	no assertion criteria provided	research
Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet	RCV000504709	SCV000926845	uncertain significance	Retinitis pigmentosa	2018-04-01	no assertion criteria provided	research
Natera, Inc.	RCV000504709	SCV001463742	uncertain significance	Retinitis pigmentosa	2020-01-06	no assertion criteria provided	clinical testing