ClinVar Miner

Submissions for variant NM_020549.5(CHAT):c.1492T>C (p.Ser498Pro)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001377468 SCV001574805 likely pathogenic Familial infantile myasthenia 2020-03-28 criteria provided, single submitter clinical testing This sequence change replaces serine with proline at codon 498 of the CHAT protein (p.Ser498Pro). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with congenital myasthenic syndrome (PMID: 21786365, Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. This variant has been reported to affect CHAT protein function (PMID: 21786365). This variant disrupts the p.Ser498 amino acid residue in CHAT. Other variant(s) that disrupt this residue have been observed in individuals with CHAT-related conditions (PMID: 11172068), which suggests that this may be a clinically significant amino acid residue. 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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