ClinVar Miner

Submissions for variant NM_001127222.2(CACNA1A):c.757C>T (p.His253Tyr) (rs121908228)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center of Genomic medicine, Geneva,University Hospital of Geneva RCV000059312 SCV000268511 likely pathogenic Episodic ataxia type 2 2016-02-19 criteria provided, single submitter clinical testing This CACNA1A variant has been identified as the likely cause of the episodic ataxia observed in the patient.
Invitae RCV001215900 SCV001387668 likely pathogenic Episodic ataxia type 2; Epileptic encephalopathy, early infantile, 42 2019-08-07 criteria provided, single submitter clinical testing This sequence change replaces histidine with tyrosine at codon 253 of the CACNA1A protein (p.His253Tyr). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with episodic ataxia type 2 in a family (PMID: 12420090). ClinVar contains an entry for this variant (Variation ID: 68442). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
UniProtKB/Swiss-Prot RCV000059312 SCV000090874 not provided Episodic ataxia type 2 no assertion provided not provided

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