ClinVar Miner

Submissions for variant NM_001127221.1(CACNA1A):c.6128C>T (p.Thr2043Met) (rs563345694)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000710970 SCV000841286 uncertain significance not provided 2016-05-24 criteria provided, single submitter clinical testing
CHLA Center for Personalized Medicine,Children's Hospital, Los Angeles RCV000735340 SCV000854493 uncertain significance Muscle weakness; Spasticity; Hypertonia; Neurogenic bladder; Spastic gait; Abnormality of the cerebral white matter; Cerebral venous thrombosis; Bone marrow hypocellularity; Myelitis; Abnormal thalamic MRI signal intensity; Abnormal brainstem MRI signal intensity; Combined immunodeficiency criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000710970 SCV000892545 uncertain significance not provided 2018-09-30 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000764178 SCV000895180 uncertain significance Episodic ataxia type 2; Spinocerebellar ataxia 6; Familial hemiplegic migraine type 1; Epileptic encephalopathy, early infantile, 42 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000710970 SCV000528222 uncertain significance not provided 2016-05-23 criteria provided, single submitter clinical testing The T2043M variant in the CACNA1A gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The T2043M variant was not observed in approximately 6100 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 T2043M 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 in mammals. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret T2043M as a variant of uncertain significance.
Invitae RCV000541910 SCV000656780 uncertain significance Episodic ataxia type 2; Epileptic encephalopathy, early infantile, 42 2018-05-18 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 2043 of the CACNA1A protein (p.Thr2043Met). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs563345694, ExAC 0.004%). This variant has not been reported in the literature in individuals with CACNA1A-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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