ClinVar Miner

Submissions for variant NM_001127222.2(CACNA1A):c.536C>T (p.Thr179Met)

gnomAD frequency: 0.00001  dbSNP: rs773461333
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000819009 SCV000959648 uncertain significance Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 2018-12-24 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). This variant has not been reported in the literature in individuals with CACNA1A-related conditions. This variant is present in population databases (rs773461333, ExAC 0.002%). This sequence change replaces threonine with methionine at codon 179 of the CACNA1A protein (p.Thr179Met). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and methionine.
CeGaT Center for Human Genetics Tuebingen RCV003411811 SCV004140238 uncertain significance not provided 2024-05-01 criteria provided, single submitter clinical testing CACNA1A: PM5, PM2:Supporting, PP2, PP3
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004526035 SCV005039951 uncertain significance not specified 2024-03-08 criteria provided, single submitter clinical testing Variant summary: CACNA1A c.536C>T (p.Thr179Met) results in a non-conservative amino acid change located in the Ion transport domain (IPR005821) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 248994 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.536C>T in individuals affected with Epileptic Encephalopathy, Early Infantile, 42 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 661567). Based on the evidence outlined above, the variant was classified as uncertain significance.

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