Submissions for variant NM_001365536.1(SCN9A):c.2827A>C (p.Met943Leu)

gnomAD frequency: 0.01339  dbSNP: rs12478318

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000080038	SCV000111932	benign	not specified	2013-09-25	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000080038	SCV000309308	likely benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000399125	SCV000418557	benign	Channelopathy-associated congenital insensitivity to pain, autosomal recessive	2018-03-06	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000461431	SCV000559256	benign	Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with febrile seizures plus, type 7	2025-02-03	criteria provided, single submitter	clinical testing
Mendelics	RCV000986924	SCV001136080	likely benign	Neuropathy, hereditary sensory and autonomic, type 2A	2019-05-28	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000992914	SCV001145512	benign	not provided	2018-12-07	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000992914	SCV001157148	benign	not provided	2023-11-02	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001129274	SCV001288789	benign	Paroxysmal extreme pain disorder	2018-03-06	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV001129275	SCV001288790	benign	Primary erythromelalgia	2018-03-06	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV000399125	SCV001435133	likely benign	Channelopathy-associated congenital insensitivity to pain, autosomal recessive		criteria provided, single submitter	research	The p.Met932Leu variant in SCN9A has been identified in at least 2 Chinese individuals with partial congenital indifference to pain (PMID: 21939494). This variant is classified as likely benign for partial congenital indifference to pain because it has been identified in >23% of Latino chromosomes and 387 total homozygotes by ExAC (http://gnomad.broadinstitute.org/).
GeneDx	RCV000992914	SCV001839022	benign	not provided	2018-11-21	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 27956748, 23895530, 25585270, 22803682, 25556685, 25250524, 21698661, 26284228, 27535533, 21939494, 23450472)
Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	RCV000080038	SCV005087985	benign	not specified	2024-07-15	criteria provided, single submitter	clinical testing	This variant is classified as Benign based on local population frequency. This variant was detected in 24% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 22. Only high quality variants are reported.
Breakthrough Genomics, Breakthrough Genomics	RCV000992914	SCV005256496	likely benign	not provided		criteria provided, single submitter	not provided
Genetic Services Laboratory, University of Chicago	RCV000080038	SCV000152670	likely benign	not specified		no assertion criteria provided	clinical testing	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed.
Gene Friend Way, National Innovation Center	RCV003313935	SCV004013893	uncertain risk allele	Autism spectrum disorder	2023-07-28	no assertion criteria provided	clinical testing	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. This variant and other mutations in SCN9A have been found in patients with familial autism (PMID: 27956748). In our study, about 10% of patients diagnosed with ASD carry this SCN9A variant.