ClinVar Miner

Submissions for variant NM_002977.3(SCN9A):c.2159T>A (p.Ile720Lys) (rs200945460)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Miraca Genetics Laboratories, RCV000191125 SCV000245533 pathogenic Primary erythromelalgia 2014-05-02 criteria provided, single submitter clinical testing This variant has been previously reported as disease-causing and was found once in our laboratory in a 61-year-old female with Bell's palsy, Melkersson-Rosenthal syndrome, right-sided trigeminal neuralgia, fibromyalgia, hyperlipidemia, hyperglycemia, thunderclap headache, similarly affected mother and siblings (not tested). Additionally, this variant has been seen twice in younger individuals without related phenotypes (a 35-year-old female and a 14-year-old male).
Genetic Services Laboratory, University of Chicago RCV000118297 SCV000152669 uncertain significance not specified 2015-04-16 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000393721 SCV000418600 likely benign Paroxysmal extreme pain disorder 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000315062 SCV000418601 likely benign Familial Febrile Seizures 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000023302 SCV000418602 likely benign Small fiber neuropathy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000393618 SCV000418603 likely benign Inherited Erythromelalgia 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000311897 SCV000418604 likely benign Congenital Indifference to Pain 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000366547 SCV000418605 likely benign Generalized epilepsy with febrile seizures plus 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000271886 SCV000418606 likely benign Severe myoclonic epilepsy in infancy 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000476046 SCV000548350 uncertain significance Hereditary sensory and autonomic neuropathy type IIA; Generalized epilepsy with febrile seizures plus, type 7 2018-12-28 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with lysine at codon 720 of the SCN9A protein (p.Ile720Lys). The isoleucine residue is moderately conserved and there is a moderate physicochemical difference between isoleucine and lysine. This variant is present in population databases (rs200945460, ExAC 0.09%). This variant has been reported in individuals affected with small fiber neuropathy, Charcot-Marie-Tooth neuropathy type 2, and erythromelalgia (PMID: 21698661, 22035805, 26392352). ClinVar contains an entry for this variant (Variation ID: 30357). Experimental studies have shown that this missense change impaired slow inactivation and reduced neurite length in dorsal root ganglion neurons (PMID: 21698661, 23280954). 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.
OMIM RCV000023302 SCV000044593 pathogenic Small fiber neuropathy 2012-01-01 no assertion criteria provided literature only

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