ClinVar Miner

Submissions for variant NM_000388.4(CASR):c.2638G>A (p.Ala880Thr)

gnomAD frequency: 0.00001  dbSNP: rs763865303
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001375498 SCV001572343 uncertain significance not specified 2021-04-06 criteria provided, single submitter clinical testing Variant summary: CASR c.2638G>A (p.Ala880Thr) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251114 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2638G>A in individuals affected with Familial Hypocalciuric Hypercalcemia and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.
Ambry Genetics RCV004037624 SCV002743352 uncertain significance Nephrolithiasis/nephrocalcinosis 2021-07-26 criteria provided, single submitter clinical testing The p.A880T variant (also known as c.2638G>A), located in coding exon 6 of the CASR gene, results from a G to A substitution at nucleotide position 2638. The alanine at codon 880 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003771217 SCV004577924 uncertain significance Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 2024-06-04 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 880 of the CASR protein (p.Ala880Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CASR-related conditions. ClinVar contains an entry for this variant (Variation ID: 1065129). 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.
Fulgent Genetics, Fulgent Genetics RCV005038156 SCV005657438 uncertain significance Familial hypocalciuric hypercalcemia 1; Neonatal severe primary hyperparathyroidism; Epilepsy, idiopathic generalized, susceptibility to, 8; Autosomal dominant hypocalcemia 1 2024-06-04 criteria provided, single submitter clinical testing

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