Submissions for variant NM_000388.4(CASR):c.638C>T (p.Ala213Val)

dbSNP: rs1559958979

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002232821	SCV000812413	uncertain significance	Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1	2018-04-17	criteria provided, single submitter	clinical testing	This sequence change replaces alanine with valine at codon 213 of the CASR protein (p.Ala213Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with CASR-related disease. 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. 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.
CeGaT Center for Human Genetics Tuebingen	RCV003326509	SCV004034016	likely pathogenic	not provided	2023-07-01	criteria provided, single submitter	clinical testing	CASR: PM2, PM5, PP2, PP4