Submissions for variant NM_001127222.2(CACNA1A):c.4035_4043del (p.1346VLR[1])

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002811312	SCV003210384	pathogenic	Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42	2024-11-04	criteria provided, single submitter	clinical testing	This variant, c.4038_4046del, results in the deletion of 3 amino acid(s) of the CACNA1A protein (p.Val1350_Arg1352del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CACNA1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 2003613). This variant disrupts a region of the CACNA1A protein in which other variant(s) (p.Arg1352Gln) have been determined to be pathogenic (PMID: 28007337, 29997391, 33425808). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV003229097	SCV003926419	uncertain significance	not provided	2022-12-09	criteria provided, single submitter	clinical testing	In-frame deletion of 3 amino acids in a non-repeat region; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge