ClinVar Miner

Submissions for variant NM_000388.4(CASR):c.1901T>C (p.Phe634Ser)

dbSNP: rs2107649591
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics RCV001663820 SCV001879538 uncertain significance not provided 2021-02-03 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV001663820 SCV002069246 likely pathogenic not provided 2018-08-30 criteria provided, single submitter clinical testing DNA sequence analysis of the CASR gene demonstrated a sequence change, c.1901T>C, in exon 7 that results in an amino acid change, p.Phe634Ser. The p.Phe634Ser change affects a highly conserved amino acid residue located in a domain of the CASR protein that is known to be functional. The p.Phe634Ser substitution appears to be deleterious using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). This particular sequence change has been previously described in the literature in another patient with familial hypocalciuric hypercalcemia (PMID: 26963950).
Labcorp Genetics (formerly Invitae), Labcorp RCV002032660 SCV002265847 uncertain significance Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 2023-04-17 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 1256478). This missense change has been observed in individual(s) with CASR-related conditions (PMID: 26963950, 32347971). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 634 of the CASR protein (p.Phe634Ser). 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. 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.

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