ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.10517C>T (p.Thr3506Met)

gnomAD frequency: 0.00002  dbSNP: rs397517966
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Total submissions: 3
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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 RCV000041670 SCV000065366 likely benign not specified 2011-07-07 criteria provided, single submitter clinical testing Thr3506Met in exon 53 of USH2A: This variant is not expected to have clinical si gnificance because computational analyses (PolyPhen, SIFT, AlignGVGD, MAPP) do n ot suggest a high likelihood of impact to the protein primarily based upon a lac k of conservation across species including mammals. Of note, chimp and orangutan have a methionine at this position despite high nearby amino acid conservation.
Counsyl RCV000669162 SCV000793882 uncertain significance Usher syndrome type 2A; Retinitis pigmentosa 39 2017-09-12 criteria provided, single submitter clinical testing
Invitae RCV001350663 SCV001545073 uncertain significance not provided 2022-07-19 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 3506 of the USH2A protein (p.Thr3506Met). This variant is present in population databases (rs397517966, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with USH2A-related conditions. ClinVar contains an entry for this variant (Variation ID: 48349). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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