ClinVar Miner

Submissions for variant NM_020549.4(CHAT):c.506T>C (p.Phe169Ser) (rs776499844)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV000761601 SCV000891764 uncertain significance Familial infantile myasthenia 2018-09-06 criteria provided, single submitter research ACMG codes: PM2, PP3, PP4
Invitae RCV000761601 SCV001570405 uncertain significance Familial infantile myasthenia 2020-09-17 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with serine at codon 169 of the CHAT protein (p.Phe169Ser). The phenylalanine residue is highly conserved and there is a large physicochemical difference between phenylalanine and serine. This variant is present in population databases (rs776499844, ExAC 0.002%). This variant has not been reported in the literature in individuals with CHAT-related conditions. ClinVar contains an entry for this variant (Variation ID: 623653). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CHAT protein function. 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.

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