Submissions for variant NM_001142800.2(EYS):c.2000G>A (p.Arg667His) (rs549456693)

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Praxis fuer Humangenetik Tuebingen	RCV000513214	SCV000609217	uncertain significance	not provided	2017-11-01	criteria provided, single submitter	clinical testing
Counsyl	RCV000670182	SCV000795009	uncertain significance	Retinitis pigmentosa 25	2017-10-24	criteria provided, single submitter	clinical testing
Invitae	RCV000513214	SCV001204999	uncertain significance	not provided	2019-12-27	criteria provided, single submitter	clinical testing	This sequence change replaces arginine with histidine at codon 667 of the EYS protein (p.Arg667His). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs549456693, ExAC 0.1%). This variant has been reported in an individual affected with retinitis pigmentosa (PMID: 28041643). 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 Clinical Services Laboratory,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.
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000504709	SCV000599147	likely pathogenic	Retinitis pigmentosa	2015-01-01	no assertion criteria provided	research
Medical Genetics Laboratory, Kennedy Center,Juliane Marie Center, Rigshospitalet	RCV000504709	SCV000926845	uncertain significance	Retinitis pigmentosa	2018-04-01	no assertion criteria provided	research