ClinVar Miner

Submissions for variant NM_206933.3(USH2A):c.10712C>T (p.Thr3571Met) (rs202175091)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000666226 SCV000790483 pathogenic Usher syndrome, type 2A; Retinitis pigmentosa 39 2017-04-04 criteria provided, single submitter clinical testing
Invitae RCV000804464 SCV000944375 pathogenic not provided 2018-12-05 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 3571 of the USH2A protein (p.Thr3571Met). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs202175091, ExAC 0.01%). This variant has been observed in individuals with Usher syndrome type II (PMID: 17085681, 21569298, 28653555, 28894305). 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: 48355). 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. For these reasons, this variant has been classified as Pathogenic.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000824782 SCV000065372 likely pathogenic Rare genetic deafness 2012-04-13 criteria provided, single submitter clinical testing This Thr3571Met variant has been identified in 12 individuals or families with U sher syndrome, 10 of whom were homozygous or compound heterozygous, and was abse nt from over 1000 controls (Jaijo 2010, Bonnet 2011, Aller 2006, Baux 2007, Na kanishi 2009, Greenstein 2012). This data suggests that this variant is likely t o be pathogenic, though additional segregation studies and/or functional analyse s are required to fully establish the pathogenicity of this variant.
SIB Swiss Institute of Bioinformatics RCV000041676 SCV000787455 likely pathogenic Usher syndrome, type 2A 2018-04-16 criteria provided, single submitter curation This variant is interpreted as a Likely Pathogenic, for Usher syndrome type 2A, Autosomal Recessive inheritance. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PM3 => For recessive disorders, detected in trans with a pathogenic variant. PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PP1 => Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease.

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