ClinVar Miner

Submissions for variant NM_001037.5(SCN1B):c.405C>G (p.Asn135Lys)

gnomAD frequency: 0.00001  dbSNP: rs372630267
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000425929 SCV000536621 uncertain significance not provided 2017-02-01 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the SCN1B gene. The N135K variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The N135K variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. However, this substitution occurs at a position where amino acids with similar properties to asparagine are tolerated across species and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.
Invitae RCV002522724 SCV003029267 uncertain significance Brugada syndrome 5 2022-05-04 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 393242). This variant has not been reported in the literature in individuals affected with SCN1B-related conditions. This variant is present in population databases (rs372630267, gnomAD 0.003%). This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 135 of the SCN1B protein (p.Asn135Lys).
CeGaT Center for Human Genetics Tuebingen RCV000425929 SCV004145412 uncertain significance not provided 2023-10-01 criteria provided, single submitter clinical testing SCN1B: PM2

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