ClinVar Miner

Submissions for variant NM_005677.4(COLQ):c.680G>A (p.Arg227Gln)

gnomAD frequency: 0.00002  dbSNP: rs764737302
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000813808 SCV000954184 uncertain significance Congenital myasthenic syndrome 5 2022-08-01 criteria provided, single submitter clinical testing Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C35"). 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. ClinVar contains an entry for this variant (Variation ID: 657237). This variant has not been reported in the literature in individuals affected with COLQ-related conditions. This variant is present in population databases (rs764737302, gnomAD 0.007%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 227 of the COLQ protein (p.Arg227Gln).
Neuberg Centre For Genomic Medicine, NCGM RCV000813808 SCV004048114 uncertain significance Congenital myasthenic syndrome 5 criteria provided, single submitter clinical testing The missense variant c.680G>A (p.Arg227Gln) in COLQ gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Arg227Gln variant is novel (not in any individuals) in 1000 Genomes and is present in the gnomAD exomes database with a frequency of 0.0004%. This variant has been reported to the ClinVar database as Uncertain Significance. The amino acid Arg at position 227 is changed to a Gln changing protein sequence and it might alter its composition and physico-chemical properties. The variant is predicted to be damaging by PolyPhen2 and the residue is conserved across species. The amino acid change p.Arg227Gln in COLQ is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance.

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