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

dbSNP: rs758554049

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Concord Molecular Medicine Laboratory, Concord Repatriation General Hospital	RCV002463981	SCV002754458	likely pathogenic	Congenital myasthenic syndrome 5	2022-11-22	criteria provided, single submitter	clinical testing	The c.1026C>G missense variant predicts an aspartic acid to glutamic acid substitution in the protein at codon 342, p.(Asp342Glu) and has been detected in trans with a pathogenic variant in a patient with CMS5, with good response to treatment with oral salbutamol. In silico analysis by REVEL suggests this variant to be damaging (score: 0.822). The variant has been described in another individual with autosomal recessive CMS5 in a compound heterozygous state [PMID: 10665486]. The c.1026C>G variant is present in a heterozygous state at a very low frequency in control population (gnomAD). The variant protein was shown to be incompetent in anchoring asymmetric AChE to the synaptic basal lamina, and patient expressed no AChE at intercostal endplates [PMID: 8390325, 14702351, 15034283]. The evidence available allows a classification of the variant as "likely pathogenic" (ACMG criteria: PS3_moderate, PM3, PM2_supporting, PP3).
Neuromuscular Department, Shariati Hospital, Tehran University of Medical Sciences	RCV003321949	SCV004027603	pathogenic	Synaptic congenital myasthenic syndromes	2023-01-01	criteria provided, single submitter	clinical testing