ClinVar Miner

Submissions for variant NM_000388.4(CASR):c.475C>G (p.Leu159Val)

dbSNP: rs767329910
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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 RCV001062371 SCV001227166 uncertain significance Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 2023-06-27 criteria provided, single submitter clinical testing This variant is present in population databases (rs767329910, gnomAD 0.0009%). 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. This variant disrupts the p.Leu159 amino acid residue in CASR. Other variant(s) that disrupt this residue have been observed in individuals with CASR-related conditions (PMID: 21175100, 27666534), which suggests that this may be a clinically significant amino acid residue. 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 tolerated. ClinVar contains an entry for this variant (Variation ID: 856823). This variant has not been reported in the literature in individuals affected with CASR-related conditions. This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 159 of the CASR protein (p.Leu159Val).
Ambry Genetics RCV004030452 SCV005035253 uncertain significance Nephrolithiasis/nephrocalcinosis 2024-02-21 criteria provided, single submitter clinical testing The p.L159V variant (also known as c.475C>G), located in coding exon 2 of the CASR gene, results from a C to G substitution at nucleotide position 475. The leucine at codon 159 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. In addition, the evidence for the gene-disease relationship is limited for pancreatitis and cancer predisposition; therefore, the clinical significance of this variant for CASR-related pancreatitis and cancer predisposition is unclear. Based on the available evidence, the clinical significance of this alteration remains unclear.

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