ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.3752T>C (p.Met1251Thr)

gnomAD frequency: 0.00003  dbSNP: rs749638533
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000474433 SCV000548785 likely benign Early infantile epileptic encephalopathy with suppression bursts 2023-08-31 criteria provided, single submitter clinical testing
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV002222515 SCV002010643 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
GeneDx RCV002222515 SCV002499936 uncertain significance not provided 2021-10-14 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Missense variants in this gene are often considered pathogenic (HGMD); This substitution is predicted to be within the transmembrane segment S2 of the third homologous domain; Has not been previously published as pathogenic or benign to our knowledge
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003993970 SCV004813805 uncertain significance not specified 2024-02-07 criteria provided, single submitter clinical testing Variant summary: SCN1A c.3752T>C (p.Met1251Thr) results in a non-conservative amino acid change located in the Ion transport domain (IPR005821) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 6.2e-06 in 1609902 control chromosomes, predominantly at a frequency of 8e-05 within the African or African-American subpopulation in the gnomAD database. 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.3752T>C in individuals affected with SCN1A-Related Seizure Disorder and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 408940). Based on the evidence outlined above, the variant was classified as uncertain significance.

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