Submissions for variant NM_001127222.2(CACNA1A):c.680T>G (p.Leu227Arg)

dbSNP: rs1057522420

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000418581	SCV000527638	uncertain significance	not provided	2018-01-30	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the CACNA1A gene. The L227R variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The L227R 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. 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	RCV000418581	SCV001151728	likely pathogenic	not provided	2019-05-01	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV001333788	SCV001526468	likely pathogenic	Spinocerebellar ataxia type 6	2018-05-15	criteria provided, single submitter	clinical testing	This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].