ClinVar Miner

Submissions for variant NM_000488.4(SERPINC1):c.1277C>G (p.Ser426Trp)

dbSNP: rs121909550
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001908898 SCV002169115 likely pathogenic Hereditary antithrombin deficiency 2024-07-08 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with tryptophan, which is neutral and slightly polar, at codon 426 of the SERPINC1 protein (p.Ser426Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with features of antithrombin III deficiency (PMID: 28174134, 29296762, 36764659; Invitae). ClinVar contains an entry for this variant (Variation ID: 1403128). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SERPINC1 protein function with a positive predictive value of 80%. This variant disrupts the p.Ser426 amino acid residue in SERPINC1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 2602168, 3512602, 3563966, 18954896, 20088933, 25298121). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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