ClinVar Miner

Submissions for variant NM_001365536.1(SCN9A):c.2129G>A (p.Cys710Tyr) (rs201709980)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000470604 SCV000548358 uncertain significance Hereditary sensory and autonomic neuropathy type IIA; Generalized epilepsy with febrile seizures plus, type 7 2020-03-12 criteria provided, single submitter clinical testing This sequence change replaces cysteine with tyrosine at codon 699 of the SCN9A protein (p.Cys699Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine. While this variant is present in population databases (rs201709980), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been reported in an individual affected with Dravet syndrome (PMID: 19763161). However, in that individual a pathogenic allele was also identified in the SCN1A gene, which suggests that this c.2096G>A variant was not the primary cause of disease. ClinVar contains an entry for this variant (Variation ID: 408580). 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: Probably Damaging; Align-GVGD: Class C0). 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.
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV001198009 SCV001368794 uncertain significance Hereditary sensory and autonomic neuropathy type IIA 2016-01-01 criteria provided, single submitter clinical testing This variant was classified as: Uncertain significance. The following ACMG criteria were applied in classifying this variant: PP3,PP4,PP5.

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