ClinVar Miner

Submissions for variant NM_000388.4(CASR):c.1238A>T (p.His413Leu)

dbSNP: rs1553766896
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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 RCV000639444 SCV000761019 uncertain significance Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 2023-04-16 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. Experimental studies have shown that this missense change does not substantially affect CASR function (PMID: 24394414). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 532598). This variant has not been reported in the literature in individuals affected with CASR-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 413 of the CASR protein (p.His413Leu).
Ambry Genetics RCV004025550 SCV002662296 uncertain significance Nephrolithiasis/nephrocalcinosis 2024-03-26 criteria provided, single submitter clinical testing The p.H413L variant (also known as c.1238A>T), located in coding exon 3 of the CASR gene, results from an A to T substitution at nucleotide position 1238. The histidine at codon 413 is replaced by leucine, an amino acid with similar properties. Limited functional analysis suggests no significant impact (Zhang C et al. J. Biol. Chem., 2014 Feb;289:5296-309). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear.

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