Submissions for variant NM_005677.4(COLQ):c.943C>T (p.Arg315Ter)

gnomAD frequency: 0.00001  dbSNP: rs121908924

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Athena Diagnostics	RCV000517951	SCV000613019	pathogenic	not provided	2016-11-04	criteria provided, single submitter	clinical testing
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV000007034	SCV001244975	pathogenic	Congenital myasthenic syndrome 5	2018-05-18	criteria provided, single submitter	clinical testing	A homozygous nonsense variant, NM_005677.3(COLQ):c.943C>T, has been identified in exon 13 of 17 of the COLQ gene. The variant is predicted to result in a premature stop codon at position 315 of the protein, NP_005668.2(COLQ):p.(Arg315*). This variant is predicted to result in loss of protein function either through truncation (including the C-terminal end region) or nonsense-mediated decay, which is a reported mechanism of pathogenicity for this gene. The variant is present in the gnomAD database at a frequency of 0.0016% (4 heterozygotes, 0 homozygotes). The variant has been previously described as pathogenic and segregated with disease in three affected members of a family (ClinVar, Ohno et al., (1999)). Additionally, functional analysis of the congenital end-pate acetylcholinesterase (AChE) showed reduced expression preventing the anchoring of the AChE to the synaptic basal lamina (Ohno et al., (1999)). Based on the information available at the time of curation, this variant has been classified as PATHOGENIC.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000007034	SCV001379932	pathogenic	Congenital myasthenic syndrome 5	2022-06-04	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 6655). This premature translational stop signal has been observed in individuals with congenital myasthenic syndrome (PMID: 10441569). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs121908924, gnomAD 0.007%). This sequence change creates a premature translational stop signal (p.Arg315*) in the COLQ gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in COLQ are known to be pathogenic (PMID: 22678886).
Revvity Omics, Revvity	RCV000007034	SCV002019701	pathogenic	Congenital myasthenic syndrome 5	2020-02-12	criteria provided, single submitter	clinical testing
Neuromuscular Department, Shariati Hospital, Tehran University of Medical Sciences	RCV003321480	SCV004027607	pathogenic	Synaptic congenital myasthenic syndromes	2023-01-01	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000007034	SCV004214468	pathogenic	Congenital myasthenic syndrome 5	2024-03-24	criteria provided, single submitter	clinical testing
OMIM	RCV000007034	SCV000027230	pathogenic	Congenital myasthenic syndrome 5	1999-09-01	no assertion criteria provided	literature only