ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.13847G>T (p.Gly4616Val)

dbSNP: rs527236124
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV001075191 SCV001240804 likely pathogenic Retinal dystrophy 2018-11-07 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002514759 SCV003524045 pathogenic not provided 2023-08-25 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 4616 of the USH2A protein (p.Gly4616Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal recessive retinitis pigmentosa (PMID: 25324289, 33105608; Invitae). ClinVar contains an entry for this variant (Variation ID: 143174). 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 expected to disrupt USH2A protein function. For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab RCV003453100 SCV004183121 likely pathogenic Retinitis pigmentosa 39 2023-11-04 criteria provided, single submitter clinical testing
Baylor Genetics RCV003453100 SCV004206442 likely pathogenic Retinitis pigmentosa 39 2022-02-03 criteria provided, single submitter clinical testing
Dept Of Ophthalmology, Nagoya University RCV001075191 SCV004707233 uncertain significance Retinal dystrophy 2023-10-01 criteria provided, single submitter research
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004525879 SCV005040051 likely pathogenic Usher syndrome 2024-03-07 criteria provided, single submitter clinical testing Variant summary: USH2A c.13847G>T (p.Gly4616Val) results in a non-conservative amino acid change located in the Fibronectin type III domain (IPR003961) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 250966 control chromosomes (gnomAD). c.13847G>T has been reported in the literature in individuals affected with retinitis pigmentosa (e.g. Oishi_2014, Koyanagi_2019, Inaba_2020, Numa_2020, Suga_2022). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 25324289, 33105608, 36284460, 31213501, 33247286). ClinVar contains an entry for this variant (Variation ID: 143174). Based on the evidence outlined above, the variant was classified as likely pathogenic.
Department of Ophthalmology and Visual Sciences Kyoto University RCV000132705 SCV000172658 probable-pathogenic Retinitis pigmentosa no assertion criteria provided not provided Converted during submission to Likely pathogenic.

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