ClinVar Miner

Submissions for variant NM_000388.4(CASR):c.662C>A (p.Pro221Gln)

dbSNP: rs397514728
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002515738 SCV003525563 uncertain significance Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 2022-04-27 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 221 of the CASR protein (p.Pro221Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with hypocalciuric hypercalcemia (PMID: 17698911, 22422767). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 60668). 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. Experimental studies have shown that this missense change affects CASR function (PMID: 22422767). This variant disrupts the p.Pro221 amino acid residue in CASR. Other variant(s) that disrupt this residue have been observed in individuals with CASR-related conditions (PMID: 11136551, 12733714, 20119591, 21645025, 25137426), which suggests that this may be a clinically significant amino acid residue. 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.
OMIM RCV000054482 SCV000082959 pathogenic Familial hypocalciuric hypercalcemia 1 2012-06-15 no assertion criteria provided literature only

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