ClinVar Miner

Submissions for variant NM_002977.3(SCN9A):c.2215A>G (p.Ile739Val) (rs182650126)

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Total submissions: 15
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Praxis fuer Humangenetik Tuebingen RCV000416064 SCV000493391 uncertain significance not provided 2017-03-31 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000416064 SCV000610459 uncertain significance not provided 2017-03-28 criteria provided, single submitter clinical testing
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000218739 SCV000297131 likely benign not specified 2015-08-19 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000218739 SCV000203531 likely benign not specified 2017-07-20 criteria provided, single submitter clinical testing
GeneDx RCV000416064 SCV000279166 uncertain significance not provided 2018-06-18 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the SCN9A gene. The I739V variant has been previously reported in the heterozygous state in multiple unrelated individuals with a clinical diagnosis of small fiber neuropathy (Faber et al., 2012; Han et al., 2012; Devigli et al., 2014). Functional studies indicate that this variant impairs channel slow inactivation and results in neuronal hyperexcitability, providing evidence to support the functional importance of this amino acid residue (Han et al., 2012). In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. However, the I739V variant is observed in 95/23890 (0.4%) alleles from individuals of Finnish background, including 2 unrelated homozygous individuals in large population cohorts and 1 homozygous individual undergoing testing at GeneDx (Lek et al., 2016). Additionally, the I739V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Genetic Services Laboratory, University of Chicago RCV000218739 SCV000596991 likely benign not specified 2017-04-05 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000324778 SCV000418593 likely benign Familial Febrile Seizures 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000379271 SCV000418594 likely benign Generalized epilepsy with febrile seizures plus 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000284837 SCV000418595 likely benign Paroxysmal extreme pain disorder 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000340033 SCV000418596 likely benign Severe myoclonic epilepsy in infancy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000398464 SCV000418597 likely benign Congenital Indifference to Pain 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000281545 SCV000418598 likely benign Inherited Erythromelalgia 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000144932 SCV000418599 likely benign Small fiber neuropathy 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000467712 SCV000559263 benign Hereditary sensory and autonomic neuropathy type IIA; Generalized epilepsy with febrile seizures plus, type 7 2018-01-02 criteria provided, single submitter clinical testing
OMIM RCV000144932 SCV000191928 pathogenic Small fiber neuropathy 2014-09-01 no assertion criteria provided literature only

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