Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000007035 | SCV001581369 | pathogenic | Congenital myasthenic syndrome 5 | 2022-11-28 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 6656). This variant has been observed in individual(s) with congenital myasthenic syndrome (PMID: 10441569, 27830186). 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. This variant is present in population databases (no rsID available, gnomAD 0.006%). This sequence change falls in intron 16 of the COLQ gene. It does not directly change the encoded amino acid sequence of the COLQ protein. It affects a nucleotide within the consensus splice site. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV002307357 | SCV002600510 | pathogenic | Congenital myasthenic syndrome | 2022-10-14 | criteria provided, single submitter | clinical testing | Variant summary: COLQ c.1298+3A>G alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: Three predict the variant abolishes the canonical 5' splicing donor site. At least one publication reports experimental evidence that this variant affects mRNA splicing resulting in skipping of exon 16 in a minigene assay (Ohno_1999). The variant allele was found at a frequency of 4.1e-06 in 241562 control chromosomes. c.1298+3A>G has been reported in the literature as a biallelic genotype in individuals affected with features of Congenital Myasthenic Syndrome (example, Ohno_1999, Wang_2016). These data indicate that the variant is likely to be associated with disease. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
OMIM | RCV000007035 | SCV000027231 | pathogenic | Congenital myasthenic syndrome 5 | 1999-09-01 | no assertion criteria provided | literature only |