ClinVar Miner

Submissions for variant NM_020549.4(CHAT):c.284C>A (p.Ala95Glu) (rs977117524)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000595736 SCV000703764 uncertain significance not provided 2018-06-26 criteria provided, single submitter clinical testing
Invitae RCV000695147 SCV000823629 uncertain significance Familial infantile myasthenia 2018-06-15 criteria provided, single submitter clinical testing This sequence change replaces alanine with glutamic acid at codon 95 of the CHAT protein (p.Ala95Glu). The alanine residue is weakly conserved and there is a moderate physicochemical difference between alanine and glutamic acid. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with CHAT-related disease. ClinVar contains an entry for this variant (Variation ID: 498640). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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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