Submissions for variant NM_001365536.1(SCN9A):c.3767A>G (p.Asn1256Ser)

gnomAD frequency: 0.00496  dbSNP: rs141268327

Total submissions: 24

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000176065	SCV000152677	likely benign	not specified	2014-09-10	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000176065	SCV000227659	likely benign	not specified	2014-11-11	criteria provided, single submitter	clinical testing
Invitae	RCV001080021	SCV000299165	benign	Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with febrile seizures plus, type 7	2024-02-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000176065	SCV000309315	likely benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000383539	SCV000418425	benign	Paroxysmal extreme pain disorder	2018-01-13	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	RCV000714847	SCV000418427	benign	Primary erythromelalgia	2018-01-13	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	RCV000389147	SCV000418428	likely benign	Inherited Erythromelalgia	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000335798	SCV000418430	likely benign	Channelopathy-associated congenital insensitivity to pain, autosomal recessive	2018-01-13	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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000422016	SCV000511746	likely benign	not provided	2016-11-07	criteria provided, single submitter	clinical testing	Converted during submission to Likely benign.
GeneDx	RCV000422016	SCV000514589	benign	not provided	2020-05-13	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 28440294, 29934995, 23895530, 29911575, 29264398, 32707200)
CeGaT Center for Human Genetics Tuebingen	RCV000422016	SCV000575255	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	SCN9A: BS2
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000422016	SCV000605066	benign	not provided	2023-10-26	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000422016	SCV000843750	benign	not provided	2018-06-21	criteria provided, single submitter	clinical testing
Genomic Research Center, Shahid Beheshti University of Medical Sciences	RCV000328939	SCV000845584	uncertain significance	Severe myoclonic epilepsy in infancy	2018-08-07	criteria provided, single submitter	clinical testing
Genomic Research Center, Shahid Beheshti University of Medical Sciences	RCV000714847	SCV000845585	uncertain significance	Primary erythromelalgia	2018-08-07	criteria provided, single submitter	clinical testing
Genomic Research Center, Shahid Beheshti University of Medical Sciences	RCV000714848	SCV000845586	uncertain significance	Neuropathy, hereditary sensory and autonomic, type 2A	2018-08-07	criteria provided, single submitter	clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000768312	SCV000898959	uncertain significance	Primary erythromelalgia; Paroxysmal extreme pain disorder; Severe myoclonic epilepsy in infancy; Channelopathy-associated congenital insensitivity to pain, autosomal recessive; Generalized epilepsy with febrile seizures plus, type 7	2018-10-22	criteria provided, single submitter	clinical testing	SCN9A NM_002977.3 exon 20 p.Asn1245Ser (c.3734A>G): This variant has been reported in the literature in 2 individuals with erythromelalgia (Zhang 2014 PMID:29911575, Haehner 2018 PMID:29934995). This variant was also seen in one individual with language impairment who also carried a second variant in SCN9A (Chen 2017 PMID:28440294). This variant is present in 0.7% (933/126946) of European alleles, including 2 homozygotes, in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/2-167094638-T-C). This variant is present in ClinVar, with several labs classifying this variant as likely benign (Variation ID:130265). However, evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Mendelics	RCV000714848	SCV001136078	likely benign	Neuropathy, hereditary sensory and autonomic, type 2A	2019-05-28	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002345422	SCV002621197	likely benign	Inborn genetic diseases	2019-09-16	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV003224155	SCV003920460	uncertain significance	Primary erythromelalgia; Paroxysmal extreme pain disorder; Channelopathy-associated congenital insensitivity to pain, autosomal recessive	2021-03-30	criteria provided, single submitter	clinical testing	SCN9A NM_002977.3 exon 20 p.Asn1245Ser (c.3734A>G): This variant has been reported in the literature in 2 individuals with erythromelalgia (Zhang 2014 PMID:29911575, Haehner 2018 PMID:29934995). This variant was also seen in one individual with language impairment who also carried a second variant in SCN9A (Chen 2017 PMID:28440294). This variant is present in 0.7% (933/126946) of European alleles, including 2 homozygotes, in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/2-167094638-T-C). This variant is present in ClinVar, with several labs classifying this variant as likely benign (Variation ID:130265). However, evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Clinical Genetics, Academic Medical Center	RCV000176065	SCV001922999	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000422016	SCV001928611	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000422016	SCV001953444	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000422016	SCV001964676	likely benign	not provided		no assertion criteria provided	clinical testing