ClinVar Miner

Submissions for variant NM_006514.3(SCN10A):c.5548C>T (p.Gln1850Ter) (rs149504103)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000494167 SCV000583012 uncertain significance not provided 2018-02-26 criteria provided, single submitter clinical testing The Q1850X variant of uncertain significance in the SCN10A gene has not been published as pathogenic or been reported as benign to our knowledge. This variant is predicted to cause loss of normal protein function by protein truncation of the final 107 amino acid residues without nonsense-mediated mRNA decay. Nevertheless, no other downstream nonsense or frameshift variants in the SCN10A gene have been reported in Human Gene Mutation Database (Stenson et al., 2014). Lastly, Q1850X has been observed in 8/66,736 (0.01%) alleles from individuals of European (non-Finnish) ancestry in the Exome Aggregation Consortium (Lek et al., 2016).
Invitae RCV000638663 SCV000760202 uncertain significance Brugada syndrome 2018-07-09 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the SCN10A gene (p.Gln1850*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 107 amino acids of the SCN10A protein. This variant is present in population databases (rs149504103, ExAC 0.01%). This variant has not been reported in the literature in individuals with SCN10A-related disease. ClinVar contains an entry for this variant (Variation ID: 430247). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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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