ClinVar Miner

Submissions for variant NM_153676.4(USH1C):c.2194A>G (p.Lys732Glu)

gnomAD frequency: 0.00014  dbSNP: rs148168494
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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 RCV000041270 SCV000064961 uncertain significance not specified 2011-11-08 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The Lys732Glu varia nt in USH1C has not been reported in the literature nor previously identified by our laboratory. However, this variant was observed in a broad population (dbSN P rs148168494) suggesting it could occur with reasonable frequency in the genera l population. Computational analyses (biochemical amino acid properties, homolog y, PolyPhen2, SIFT, AlignGVGD) do not provide strong support for or against path ogenicity. In summary, the clinical significance of this variant cannot be deter mined at this time; however, based on identification of this variant in this ind ividual who has another cause for their clinical features and in dbSNP we would lean towards a more likely benign role.
Counsyl RCV000666460 SCV000790757 uncertain significance Usher syndrome type 1C; Autosomal recessive nonsyndromic hearing loss 18A 2017-04-24 criteria provided, single submitter clinical testing
Invitae RCV002513578 SCV003480317 uncertain significance not provided 2022-07-03 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 432 of the USH1C protein (p.Lys432Glu). This variant is present in population databases (rs148168494, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with USH1C-related conditions. ClinVar contains an entry for this variant (Variation ID: 47994). 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: "Benign"; Align-GVGD: "Class C0"). 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.
Natera, Inc. RCV001826585 SCV002083709 uncertain significance Usher syndrome type 1C 2020-07-08 no assertion criteria provided clinical testing

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