ClinVar Miner

Submissions for variant NM_001365536.1(SCN9A):c.4503+1G>T (rs746241591)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000236300 SCV000293022 pathogenic not provided 2015-08-18 criteria provided, single submitter clinical testing The c.4470+1 G>T splice site variant in the SCN9A gene destroys the canonical splice donor site in intron 25. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. Although this variant has not been previously reported to our knowledge, it is considered a disease-causing mutation.
Invitae RCV000694025 SCV000822450 likely pathogenic Hereditary sensory and autonomic neuropathy type IIA; Generalized epilepsy with febrile seizures plus, type 7 2020-08-30 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 25 of the SCN9A gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs746241591, ExAC 0.002%). This variant has not been reported in the literature in individuals with SCN9A-related disease. ClinVar contains an entry for this variant (Variation ID: 245854). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SCN9A are known to be pathogenic (PMID: 17470132, 19304393). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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