ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.13010C>T (p.Thr4337Met) (rs527236137)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare 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.
Invitae RCV001043740 SCV001207501 pathogenic not provided 2019-11-29 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 4337 of the USH2A protein (p.Thr4337Met). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in multiple individuals with clinical features of Usher syndrome or retinitis pigmentosa (PMID: 17085681, 24498627, 26667666, 25356976, 29588463, 28944237, 26654877, 25324289, Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 143172). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). 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 Praxis fuer Humangenetik Tuebingen RCV001043740 SCV001246242 pathogenic not provided 2018-01-01 criteria provided, single submitter clinical testing
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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