Submissions for variant NM_000069.3(CACNA1S):c.482T>C (p.Val161Ala)

gnomAD frequency: 0.00003  dbSNP: rs141521945

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000522368	SCV000620981	uncertain significance	not provided	2017-09-18	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the CACNA1S gene. The V161A variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The V161A variant is observed in 9/66722 (0.01%) alleles from individuals of European background, including 9 unrelated heterozygous individuals in the ExAC dataset (Lek et al., 2016). The V161A variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Valine are tolerated across species. However, in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000801970	SCV000941776	likely benign	Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility to, 5	2024-12-17	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV003159691	SCV003870762	uncertain significance	Inborn genetic diseases	2023-01-31	criteria provided, single submitter	clinical testing	The c.482T>C (p.V161A) alteration is located in exon 4 (coding exon 4) of the CACNA1S gene. This alteration results from a T to C substitution at nucleotide position 482, causing the valine (V) at amino acid position 161 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.