Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000524604 | SCV000638073 | uncertain significance | Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 | 2023-12-12 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 14 of the CASR protein (p.Thr14Ala). This variant is present in population databases (rs199515839, gnomAD 0.004%). This missense change has been observed in individual(s) with primary hyperparathyroidism (PMID: 15879434). ClinVar contains an entry for this variant (Variation ID: 463950). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Experimental studies have shown that this missense change does not substantially affect CASR function (PMID: 15879434). 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. |
Gene |
RCV001770431 | SCV001993418 | uncertain significance | not provided | 2020-02-27 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate no damaging effect on protein expression, processing, and localization, or response to extracellular calcium (Pidasheva 2005); Observed in individuals with a personal or family history including parathyroid adenoma (Pidasheva 2005); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 17274009, 15879434, 17320849) |
Fulgent Genetics, |
RCV002483414 | SCV002776051 | uncertain significance | Familial hypocalciuric hypercalcemia 1; Neonatal severe primary hyperparathyroidism; Epilepsy, idiopathic generalized, susceptibility to, 8; Autosomal dominant hypocalcemia 1 | 2021-11-29 | criteria provided, single submitter | clinical testing | |
Center for Genomic Medicine, |
RCV003320679 | SCV004024942 | uncertain significance | not specified | 2023-08-15 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV004023965 | SCV005034806 | likely benign | Nephrolithiasis/nephrocalcinosis | 2023-12-27 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |