Submissions for variant NM_206933.4(USH2A):c.14020A>G (p.Arg4674Gly)

dbSNP: rs80338904

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001379272	SCV001577043	likely pathogenic	not provided	2022-07-27	criteria provided, single submitter	clinical testing	This variant is not present in population databases (gnomAD no frequency). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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 disruptive. ClinVar contains an entry for this variant (Variation ID: 2362). This missense change has been observed in individual(s) with retinitis pigmentosa (PMID: 17296898, 31456290). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 4674 of the USH2A protein (p.Arg4674Gly).
OMIM	RCV000002458	SCV000022616	pathogenic	Retinitis pigmentosa 39	2007-02-01	no assertion criteria provided	literature only
GeneReviews	RCV000032522	SCV000056185	not provided	Retinitis pigmentosa		no assertion provided	literature only
Sharon lab, Hadassah-Hebrew University Medical Center	RCV000032522	SCV001161334	likely pathogenic	Retinitis pigmentosa	2019-06-23	no assertion criteria provided	research