Submissions for variant NM_001368882.1(COL13A1):c.1285-1G>C

gnomAD frequency: 0.00003  dbSNP: rs763197055

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001377822	SCV001575257	likely pathogenic	not provided	2022-07-15	criteria provided, single submitter	clinical testing	In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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: 1066742). This variant has not been reported in the literature in individuals affected with COL13A1-related conditions. This variant is present in population databases (rs763197055, gnomAD 0.02%). This sequence change affects an acceptor splice site in intron 23 of the COL13A1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in COL13A1 are known to be pathogenic (PMID: 26626625).
Revvity Omics, Revvity	RCV003136050	SCV003825104	likely pathogenic	Congenital myasthenic syndrome 19	2022-06-21	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003136050	SCV005395665	likely pathogenic	Congenital myasthenic syndrome 19	2024-09-05	criteria provided, single submitter	clinical testing	Variant summary: COL13A1 c.1252-1G>C is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing and loss of COL13A1 function. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a 3' acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 3.3e-05 in 214742 control chromosomes. To our knowledge, no occurrence of c.1252-1G>C in individuals affected with Congenital Myasthenic Syndrome 19 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 1066742). Based on the evidence outlined above, the variant was classified as likely pathogenic.