ClinVar Miner

Submissions for variant NM_005677.4(COLQ):c.1321A>G (p.Thr441Ala)

gnomAD frequency: 0.00003  dbSNP: rs375215281
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000517041 SCV000613018 likely pathogenic not provided 2016-11-04 criteria provided, single submitter clinical testing
Invitae RCV000644599 SCV000766299 pathogenic Congenital myasthenic syndrome 5 2023-05-08 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 447217). This missense change has been observed in individuals with congenital myasthenic syndrome (PMID: 15248101, 18180250, 22678886). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs375215281, gnomAD 0.006%). This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 441 of the COLQ protein (p.Thr441Ala).
Revvity Omics, Revvity RCV000644599 SCV002023366 likely pathogenic Congenital myasthenic syndrome 5 2020-02-06 criteria provided, single submitter clinical testing
MGZ Medical Genetics Center RCV000644599 SCV002580013 likely pathogenic Congenital myasthenic syndrome 5 2022-05-30 criteria provided, single submitter clinical testing
GeneDx RCV000517041 SCV004021312 uncertain significance not provided 2023-01-20 criteria provided, single submitter clinical testing Reported with a second COLQ variant, phase unknown, in a patient with ptosis, pain, and muscle weakness (Wargon et al., 2012); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 31589614, 31773638, 32528171, 18180250, 34553317, 15248101, 22088788)
Baylor Genetics RCV000644599 SCV004214432 likely pathogenic Congenital myasthenic syndrome 5 2023-10-31 criteria provided, single submitter clinical testing

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