Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000155312 | SCV000204998 | uncertain significance | not specified | 2013-07-26 | criteria provided, single submitter | clinical testing | The Gln747Arg variant in USH1C has not been identified in individuals with heari ng loss, but has been identified in 0.02% (1/4400) of African American chromosom es from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs. washington.edu/EVS/; dbSNP rs201600193). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogeni c role. Computational analyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein. It should be noted that this variant occurs in exon 20 o f USH1C that is expressed in the ear and not the eye and therefore would likely only be relevant to nonsyndromic hearing loss, not Usher syndrome. In summary, a dditional data is needed to determine the clinical significance of this variant. |
Counsyl | RCV000668570 | SCV000793195 | uncertain significance | Usher syndrome type 1C; Autosomal recessive nonsyndromic hearing loss 18A | 2017-08-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV002514993 | SCV003511132 | uncertain significance | not provided | 2022-06-27 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 447 of the USH1C protein (p.Gln447Arg). This variant is present in population databases (rs201600193, 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: 178564). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; 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, |
RCV001272252 | SCV001454056 | uncertain significance | Usher syndrome type 1C | 2020-09-16 | no assertion criteria provided | clinical testing |