Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular 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 . |
Gene |
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, |
RCV001831696 | SCV002077568 | uncertain significance | Usher syndrome type 1C | 2019-11-11 | no assertion criteria provided | clinical testing |