Total submissions: 3
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, |
RCV000497658 | SCV000590871 | uncertain significance | not specified | 2015-12-30 | criteria provided, single submitter | clinical testing | |
Genomics England Pilot Project, |
RCV001542562 | SCV001760102 | likely pathogenic | Neonatal severe primary hyperparathyroidism | no assertion criteria provided | clinical testing |