ClinVar Miner

Submissions for variant NM_153676.4(USH1C):c.2458G>A (p.Ala820Thr)

gnomAD frequency: 0.00003  dbSNP: rs397517878
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Total submissions: 4
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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 RCV000041280 SCV000064971 uncertain significance not specified 2011-10-10 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The Ala820Thr varia nt in USH1C has not been reported in the literature nor previously identified by our laboratory. Computational analyses (biochemical amino acid properties, Poly Phen2, SIFT, AlignGVGD) do not provide strong support for pathogenicity. However , this information is not accurate enough to rule out pathogenicity. In the abse nce of additional information, such as identification of a second USH1C variant in this individual, control data, segregation studies or functional analysis, th e clinical significance of this variant cannot be determined at this time; howev er, we would lean towards a more likely benign role given the computational pred iction assessment.
Counsyl RCV000669772 SCV000794555 uncertain significance Usher syndrome type 1C; Autosomal recessive nonsyndromic hearing loss 18A 2017-09-28 criteria provided, single submitter clinical testing
Invitae RCV001852839 SCV002303996 uncertain significance not provided 2021-09-17 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 520 of the USH1C protein (p.Ala520Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs397517878, ExAC 0.006%). This variant has not been reported in the literature in individuals with USH1C-related conditions. ClinVar contains an entry for this variant (Variation ID: 48004). 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
GeneDx RCV001852839 SCV002758847 uncertain significance not provided 2022-06-01 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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