Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001054181 | SCV001218484 | uncertain significance | Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 | 2022-10-16 | criteria provided, single submitter | clinical testing | 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. 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 disruptive. ClinVar contains an entry for this variant (Variation ID: 850090). This missense change has been observed in individual(s) with familial hypocalciuric hypercalcemia (PMID: 22422767, 31433865, 32761341). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 778 of the CASR protein (p.Gly778Arg). |
Gene |
RCV001847141 | SCV002104318 | uncertain significance | not provided | 2022-02-25 | criteria provided, single submitter | clinical testing | Identified in patients with familial hypocalciuric hypercalcemia in published literature (Khairi et al., 2020; Hannan et al., 2012) and classified as both a variant of uncertain significance and as a pathogenic variant; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 22422767, 32761341) |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003230626 | SCV003928957 | uncertain significance | not specified | 2023-04-15 | criteria provided, single submitter | clinical testing | Variant summary: CASR c.2332G>C (p.Gly778Arg) results in a non-conservative amino acid change located in the GPCR family 3, C-terminal domain (IPR017978) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251070 control chromosomes (gnomAD). c.2332G>C has been reported in the literature in individuals affected with Familial Hypocalciuric Hypercalcemia (e.g. Hannan_2012, Nissen_2019, Khairi_2020). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters have assessed the variant since 2014: both classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |