Submissions for variant NM_001127222.2(CACNA1A):c.3683C>T (p.Thr1228Met)

gnomAD frequency: 0.00001  dbSNP: rs1057518532

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000413498	SCV000492271	uncertain significance	not specified	2016-12-06	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the CACNA1A gene. The T1229M variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The T1229M variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The T1229M variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, missense variants in nearby residues have not been reported in Human Gene Mutation Database in association with CACNA1A-related disorders (Stenson et al., 2014). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
CeGaT Center for Human Genetics Tuebingen	RCV000658822	SCV000780618	uncertain significance	not provided	2024-02-01	criteria provided, single submitter	clinical testing	CACNA1A: PM2:Supporting, PP2, PS2:Supporting