ClinVar Miner

Submissions for variant NM_002977.3(SCN9A):c.2428G>A (p.Val810Met) (rs41268671)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000498158 SCV000589358 uncertain significance not provided 2017-04-13 criteria provided, single submitter clinical testing The V810M variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The V810M variant is observed in 13/16468 (0.08%) alleles from individuals of South Asian background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The V810M variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Valine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Illumina Clinical Services Laboratory,Illumina RCV000293857 SCV000418572 likely benign Severe myoclonic epilepsy in infancy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000348802 SCV000418573 likely benign Generalized epilepsy with febrile seizures plus 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000384589 SCV000418574 likely benign Small fiber neuropathy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000290307 SCV000418575 likely benign Familial Febrile Seizures 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000344215 SCV000418576 likely benign Paroxysmal extreme pain disorder 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000402179 SCV000418577 likely benign Congenital Indifference to Pain 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000285786 SCV000418578 likely benign Inherited Erythromelalgia 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000240135 SCV000299168 uncertain significance Hereditary sensory and autonomic neuropathy type IIA; Generalized epilepsy with febrile seizures plus, type 7 2017-07-21 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 810 of the SCN9A protein (p.Val810Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs41268671, ExAC 0.08%). This variant has been reported in an individual with clinically-suspected inherited peripheral neuropathy (PMID: 26392352). ClinVar contains an entry for this variant (Variation ID: 254095). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, this is a rare missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.

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