Submissions for variant NM_006514.4(SCN10A):c.5548C>T (p.Gln1850Ter)

gnomAD frequency: 0.00010  dbSNP: rs149504103

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000494167	SCV000583012	uncertain significance	not provided	2020-01-28	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID#430247; Landrum et al., 2016); Nonsense variant predicted to result in protein truncation, although loss-of-function variants have not been reported downstream of this position in the protein
Labcorp Genetics (formerly Invitae), Labcorp	RCV000638663	SCV000760202	uncertain significance	Brugada syndrome	2022-08-23	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln1850*) in the SCN10A gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 107 amino acid(s) of the SCN10A protein. This variant is present in population databases (rs149504103, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with SCN10A-related conditions. 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. 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.
Ambry Genetics	RCV002350103	SCV002648787	likely benign	Cardiovascular phenotype	2022-07-18	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Fulgent Genetics, Fulgent Genetics	RCV002506197	SCV002816361	uncertain significance	Episodic pain syndrome, familial, 2	2021-09-28	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000494167	SCV001924851	uncertain significance	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000494167	SCV001952665	uncertain significance	not provided		no assertion criteria provided	clinical testing