ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.13010C>T (p.Thr4337Met)

dbSNP: rs527236137
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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000824779 SCV000271291 likely pathogenic Rare genetic deafness 2015-05-14 criteria provided, single submitter clinical testing The p.Thr4337Met variant in USH2A has been previously reported in 5 probands wit h Usher syndrome and 2 probands with retinitis pigmentosa (Aller 2006, McGee 201 0, Besnard 2014, Baux 2014, Lenassi 2015). Two of the probands with Usher syndr ome were compound heterozygotes with a second pathogenic or likely pathogenic va riant, and the two probands with retinitis pigmentosa were both compound heteroz ygous with a second pathogenic variant. This variant has not been identified in large population studies. Computational prediction tools and conservation analy sis do not provide strong support for or against an impact to the protein. In su mmary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic based on multiple reported occur rences with pathogenic USH2A variants in individuals with Usher syndrome.
Labcorp Genetics (formerly Invitae), Labcorp RCV001043740 SCV001207501 pathogenic not provided 2024-01-09 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 4337 of the USH2A protein (p.Thr4337Met). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of Usher syndrome or retinitis pigmentosa (PMID: 17085681, 24498627, 25324289, 25356976, 26654877, 26667666, 28944237, 29588463; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 143172). 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 with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV001073283 SCV001238819 pathogenic Retinal dystrophy 2018-10-15 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001043740 SCV001246242 pathogenic not provided 2018-01-01 criteria provided, single submitter clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV001043740 SCV001762261 pathogenic not provided 2021-06-17 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV001043740 SCV002021611 likely pathogenic not provided 2021-08-26 criteria provided, single submitter clinical testing
Ophthalmic Genetics Group, Institute of Molecular and Clinical Ophthalmology Basel RCV003324517 SCV004030332 pathogenic Retinitis pigmentosa 2023-07-24 criteria provided, single submitter research Clinical significance based on ACMG v2.0
Genome-Nilou Lab RCV000983996 SCV004181915 likely pathogenic Retinitis pigmentosa 39 2023-11-04 criteria provided, single submitter clinical testing
Baylor Genetics RCV000983996 SCV004208147 pathogenic Retinitis pigmentosa 39 2024-02-13 criteria provided, single submitter clinical testing
Dept Of Ophthalmology, Nagoya University RCV001073283 SCV004707253 pathogenic Retinal dystrophy 2023-10-01 criteria provided, single submitter research
Department of Ophthalmology and Visual Sciences Kyoto University RCV000132703 SCV000172656 pathogenic Usher syndrome type 2A no assertion criteria provided not provided Converted during submission to Pathogenic.
Counsyl RCV000983996 SCV000790257 pathogenic Retinitis pigmentosa 39 2017-03-24 no assertion criteria provided clinical testing

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