ClinVar Miner

Submissions for variant NM_000388.4(CASR):c.416T>C (p.Ile139Thr)

dbSNP: rs1060502860
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV002230098 SCV000550996 uncertain significance Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1 2021-04-14 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 139 of the CASR protein (p.Ile139Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in individual(s) with hypoparathyroidism (PMID: 31433868). This variant is not present in population databases (ExAC no frequency).
Molecular Diagnostics Lab, Nemours Children's Health, Delaware RCV000497658 SCV000590871 uncertain significance not specified 2015-12-30 criteria provided, single submitter clinical testing
Genomics England Pilot Project, Genomics England RCV001542562 SCV001760102 likely pathogenic Neonatal severe primary hyperparathyroidism no assertion criteria provided clinical testing

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