Submissions for variant NM_006514.4(SCN10A):c.1430C>T (p.Pro477Leu)

gnomAD frequency: 0.00039  dbSNP: rs142235256

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001081469	SCV000289548	likely benign	Brugada syndrome	2025-01-17	criteria provided, single submitter	clinical testing
GeneDx	RCV000231917	SCV001795912	likely benign	not provided	2020-09-24	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics	RCV002392710	SCV002702787	likely benign	Cardiovascular phenotype	2019-11-25	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	RCV002487079	SCV002802255	likely benign	Episodic pain syndrome, familial, 2	2021-09-13	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV005238765	SCV005883862	likely benign	not specified	2024-12-03	criteria provided, single submitter	clinical testing	Variant summary: SCN10A c.1430C>T (p.Pro477Leu) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00052 in 251480 control chromosomes, predominantly at a frequency of 0.00091 within the Non-Finnish European subpopulation in the gnomAD database. The allele frequency suggests that the variant is likely not associated with high a penetrance, severe, dominant disease phenotype. To our knowledge, no occurrence of c.1430C>T in individuals affected with Episodic pain syndrome, familial, 2 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 240663). Based on the evidence outlined above, the variant was classified as likely benign.
Clinical Genetics, Academic Medical Center	RCV000231917	SCV001917316	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000231917	SCV001959307	likely benign	not provided		no assertion criteria provided	clinical testing