ClinVar Miner

Submissions for variant NM_000388.4(CASR):c.1412A>T (p.Asn471Ile)

gnomAD frequency: 0.00001  dbSNP: rs145042469
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000686954 SCV000814497 uncertain significance Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 2023-11-02 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 471 of the CASR protein (p.Asn471Ile). This variant is present in population databases (rs145042469, gnomAD 0.002%). 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: 566997). 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. 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.
Ambry Genetics RCV002319081 SCV001171794 uncertain significance Inborn genetic diseases; Nephrolithiasis/nephrocalcinosis 2019-01-18 criteria provided, single submitter clinical testing The p.N471I variant (also known as c.1412A>T), located in coding exon 4 of the CASR gene, results from an A to T substitution at nucleotide position 1412. The asparagine at codon 471 is replaced by isoleucine, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. 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.
GeneDx RCV001756161 SCV001997052 uncertain significance not provided 2019-12-09 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge

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