ClinVar Miner

Submissions for variant NM_153676.4(USH1C):c.592A>T (p.Ser198Cys)

gnomAD frequency: 0.00005  dbSNP: rs141771249
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Total submissions: 5
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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 RCV000041299 SCV000064990 uncertain significance not specified 2012-04-17 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The Ser198Cys varia nt in USH1C has not been reported in the literature nor previously identified by our laboratory. However, this variant has been identified in 1/7020 (0.01%) Eur opean American chromosomes and 1/3108 (0.0%) African American chromosomes from a broad population (NHLBI Exome Sequencing Project; http://evs.gs.washington.edu/ EVS). Computational analyses (biochemical amino acid properties, conservation, P olyPhen2, and SIFT) suggest that the Ser198Cys variant may not impact the protei n, particularly based upon lack of conservation even in mammals, though this inf ormation is not predictive enough to rule out pathogenicity. In summary, the cli nical significance of this variant cannot be determined with certainty; however based upon lack of conservation, we would lean towards a more likely benign role .
GeneDx RCV002472946 SCV002770115 uncertain significance not provided 2022-06-20 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Invitae RCV002472946 SCV003521671 uncertain significance not provided 2024-01-19 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 198 of the USH1C protein (p.Ser198Cys). This variant is present in population databases (rs141771249, gnomAD 0.02%). 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: 48022). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
Ambry Genetics RCV003258661 SCV003946281 uncertain significance Inborn genetic diseases 2023-03-27 criteria provided, single submitter clinical testing The c.592A>T (p.S198C) alteration is located in exon 8 (coding exon 8) of the USH1C gene. This alteration results from a A to T substitution at nucleotide position 592, causing the serine (S) at amino acid position 198 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001831696 SCV002077568 uncertain significance Usher syndrome type 1C 2019-11-11 no assertion criteria provided clinical testing

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