Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001952881 | SCV002222088 | uncertain significance | Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 | 2021-05-12 | 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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 C45"). This variant has not been reported in the literature in individuals with CASR-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with glutamine at codon 636 of the CASR protein (p.Lys636Gln). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and glutamine. |
Ambry Genetics | RCV004043170 | SCV002719922 | uncertain significance | Nephrolithiasis/nephrocalcinosis | 2022-04-21 | criteria provided, single submitter | clinical testing | The p.K636Q variant (also known as c.1906A>C), located in coding exon 6 of the CASR gene, results from an A to C substitution at nucleotide position 1906. The lysine at codon 636 is replaced by glutamine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |