ClinVar Miner

Submissions for variant NM_001127222.2(CACNA1A):c.4979G>A (p.Arg1660His) (rs121908216)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000517293 SCV000612549 likely pathogenic not provided 2020-11-19 criteria provided, single submitter clinical testing This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). This variant appears to be associated with disease in at least one family, however, the available information does not rule out an apparent association due to chance. Computational tools predict that this variant is damaging.
GeneDx RCV000517293 SCV000617514 likely pathogenic not provided 2019-10-10 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect This variant is associated with the following publications: (PMID: 29482223, 28742085, 10987655, 26814174, 11814735, 11179022, 16325861)
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV000009017 SCV000886432 likely pathogenic Episodic ataxia type 2 2018-10-23 criteria provided, single submitter research
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000517293 SCV001480076 pathogenic not provided 2021-02-01 criteria provided, single submitter clinical testing
Invitae RCV001381850 SCV001580407 pathogenic Episodic ataxia type 2; Epileptic encephalopathy, early infantile, 42 2020-06-12 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 1661 of the CACNA1A protein (p.Arg1661His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of, or diagnosis of, episodic ataxia (PMID: 10987655, 29482223). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 8495). 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. For these reasons, this variant has been classified as Pathogenic.
Genomics England Pilot Project,Genomics England RCV001542800 SCV001760436 likely pathogenic Spinocerebellar ataxia type 6 criteria provided, single submitter clinical testing
OMIM RCV000009017 SCV000029232 pathogenic Episodic ataxia type 2 1999-09-01 no assertion criteria provided literature only
UniProtKB/Swiss-Prot RCV000009017 SCV000090859 not provided Episodic ataxia type 2 no assertion provided not provided
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000517293 SCV001929906 pathogenic not provided no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000517293 SCV001958634 likely pathogenic not provided no assertion criteria provided clinical testing

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