ClinVar Miner

Submissions for variant NM_000388.4(CASR):c.10T>C (p.Tyr4His)

dbSNP: rs1559955224
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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 RCV002233448 SCV000836456 uncertain significance Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 2021-07-28 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with CASR-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces tyrosine with histidine at codon 4 of the CASR protein (p.Tyr4His). The tyrosine residue is moderately conserved and there is a moderate physicochemical difference between tyrosine and histidine.
Ambry Genetics RCV004026752 SCV002742649 uncertain significance Nephrolithiasis/nephrocalcinosis 2024-01-09 criteria provided, single submitter clinical testing The p.Y4H variant (also known as c.10T>C), located in coding exon 1 of the CASR gene, results from a T to C substitution at nucleotide position 10. The tyrosine at codon 4 is replaced by histidine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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