ClinVar Miner

Submissions for variant NM_020549.5(CHAT):c.1321G>A (p.Glu441Lys)

gnomAD frequency: 0.00001  dbSNP: rs121912816
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000019059 SCV001199619 uncertain significance Familial infantile myasthenia 2023-11-24 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 441 of the CHAT protein (p.Glu441Lys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with congenital myasthenic syndrome (PMID: 11172068). ClinVar contains an entry for this variant (Variation ID: 17507). 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 with a positive predictive value of 95%. Experimental studies have shown that this missense change affects CHAT function (PMID: 11172068). 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.
Baylor Genetics RCV000019059 SCV004215801 likely pathogenic Familial infantile myasthenia 2023-10-11 criteria provided, single submitter clinical testing
OMIM RCV000019059 SCV000039346 pathogenic Familial infantile myasthenia 2001-02-13 no assertion criteria provided literature only

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