Submissions for variant NM_001127222.2(CACNA1A):c.3411dup (p.Lys1138fs)

dbSNP: rs746790849

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Center for Human Genetics Tuebingen	RCV000996788	SCV001151710	likely pathogenic	not provided	2019-04-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV003769356	SCV004571369	pathogenic	Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42	2024-01-11	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Lys1139Glnfs*6) in the CACNA1A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CACNA1A are known to be pathogenic (PMID: 10371528, 19486177, 25735478, 27250579). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with episodic ataxia (PMID: 12736095). This variant is also known as Insertion C after 3689. ClinVar contains an entry for this variant (Variation ID: 808473). For these reasons, this variant has been classified as Pathogenic.
Research Unit of Clinical Neuroscience, Medical Research Center Oulu, University of Oulu	RCV001553543	SCV001774430	likely pathogenic	Episodic ataxia type 2	2021-07-06	no assertion criteria provided	research	The variant was found in a patient with dominantly inherited ataxia. The mutation causes a frameshift and early termination of the protein suggesting pathogenicity. However, functional studies and segregation analyses are required to confirm the pathogenicity of the variant.