Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Baylor Genetics | RCV000679939 | SCV000807373 | uncertain significance | Migraine, familial hemiplegic, 1 | 2017-09-01 | criteria provided, single submitter | clinical testing | Likely pathogenicity based on finding it once in our laboratory de novo in a 9-year-old male with intellectual disability, epilepsy, intermittent hemiplegic attacks, mild ataxia. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV005056423 | SCV005726170 | likely pathogenic | Developmental and epileptic encephalopathy, 42 | 2024-11-19 | criteria provided, single submitter | clinical testing | Variant summary: CACNA1A c.689G>T (p.Gly230Val) results in a non-conservative amino acid change located in the Ion transport protein 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 was absent in 249000 control chromosomes (gnomAD). c.689G>T has been reported in the literature in at least one individual affected with Epileptic Encephalopathy and observed as de novo (Jiang_2019). At least one publication reports experimental evidence evaluating an impact on protein function and this variant results in loss of function effects with reduced whole cell current densities and decreased channel expression at the cell membrane (Jiang_2019). The following publications have been ascertained in the context of this evaluation (PMID: 31468518, 35600082, 34068417, 37422902). ClinVar contains an entry for this variant (Variation ID: 560966). Based on the evidence outlined above, the variant was classified as likely pathogenic. |