ClinVar Miner

Submissions for variant NM_000388.4(CASR):c.367T>A (p.Leu123Met)

dbSNP: rs2107627702
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002016645 SCV002302040 uncertain significance Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 2022-09-07 criteria provided, single submitter clinical testing Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. ClinVar contains an entry for this variant (Variation ID: 1511340). This missense change has been observed in individual(s) with CASR-related conditions (PMID: 30407919). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 123 of the CASR protein (p.Leu123Met).
Ambry Genetics RCV004990573 SCV005550167 uncertain significance Nephrolithiasis/nephrocalcinosis 2024-07-05 criteria provided, single submitter clinical testing The p.L123M variant (also known as c.367T>A), located in coding exon 2 of the CASR gene, results from a T to A substitution at nucleotide position 367. The leucine at codon 123 is replaced by methionine, an amino acid with highly similar properties. This alteration was identified in an individual diagnosed with hypocalcemia (García-Castaño A et al. Eur J Endocrinol, 2019 Jan;180:59-70). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.
Fulgent Genetics, Fulgent Genetics RCV005032112 SCV005657380 uncertain significance Familial hypocalciuric hypercalcemia 1; Neonatal severe primary hyperparathyroidism; Epilepsy, idiopathic generalized, susceptibility to, 8; Autosomal dominant hypocalcemia 1 2024-04-02 criteria provided, single submitter clinical testing

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