ClinVar Miner

Submissions for variant NM_006514.3(SCN10A):c.724T>A (p.Ser242Thr) (rs140288103)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Fulgent Genetics,Fulgent Genetics RCV000764504 SCV000895575 uncertain significance Episodic pain syndrome, familial, 2 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000523846 SCV000617396 uncertain significance not provided 2017-09-01 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the SCN10A gene. The S242T variant has been previously reported in a male diagnosed with Brugada syndrome at 20 years of age, who had a history of syncope and sudden cardiac death (Hu et al., 2014); however, no segregation studies were completed. This variant has also been observed in 24/66436 (0.04%) alleles from individuals of Non-Finnish European ancestry in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Additionally, S242T is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Nevertheless, this substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function.
Invitae RCV000556288 SCV000637042 uncertain significance Brugada syndrome 2018-08-10 criteria provided, single submitter clinical testing This sequence change replaces serine with threonine at codon 242 of the SCN10A protein (p.Ser242Thr). The serine residue is highly conserved and there is a small physicochemical difference between serine and threonine. This variant is present in population databases (rs140288103, ExAC 0.04%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been reported in an individual affected with Brugada syndrome. Currently there is insufficient evidence to conclude whether this variant segregates with disease or not (PMID: 24998131). ClinVar contains an entry for this variant (Variation ID: 449360). 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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