ClinVar Miner

Submissions for variant NM_005677.4(COLQ):c.1026C>A (p.Asp342Glu)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003880718 SCV004688324 likely pathogenic Congenital myasthenic syndrome 5 2023-12-10 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 342 of the COLQ protein (p.Asp342Glu). This variant is present in population databases (rs758554049, gnomAD 0.003%). This missense change has been observed in individual(s) with congenital myasthenic syndrome (PMID: 10665486). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. 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 not expected to disrupt COLQ protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects COLQ function (PMID: 10665486, 14702351). 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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