ClinVar Miner

Submissions for variant NM_001330260.2(SCN8A):c.971G>A (p.Cys324Tyr)

dbSNP: rs2138739035
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV002273059 SCV002557638 likely pathogenic Developmental and epileptic encephalopathy, 13 2023-07-16 criteria provided, single submitter clinical testing Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Likely pathogenic. Following criteria are met: 0103 - Loss of function and gain of function are known mechanisms of disease in this gene, and are associated with cognitive impairment with or without cerebellar ataxia (MIM#614306), and developmental and epileptic encephalopathy 13 (MIM#614558), respectively. In addition, gain of function is speculated for benign familial infantile seizures, 5 (MIM#617080) (PMID: 31904124, OMIM). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from cysteine to tyrosine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0603 - Missense variant in a region that is highly intolerant to missense variation (high constraint region in DECIPHER). (SP) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0802 - This variant has moderate previous evidence of pathogenicity in an unrelated individual. This variant has been reported de novo in an individual with early infantile epileptic encephalopathy (PMID: 35599849). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1207 - Parental origin of the variant is unresolved. Subsequent analysis has shown that this variant is not maternally inherited; however, a sample from this individual's father has not been tested. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
University of British Columbia, BC Children's Hospital RCV003325437 SCV004031481 pathogenic Cognitive impairment with or without cerebellar ataxia 2023-08-30 criteria provided, single submitter research

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