ClinVar Miner

Submissions for variant NM_000093.5(COL5A1):c.5294G>A (p.Arg1765His)

gnomAD frequency: 0.00002  dbSNP: rs150608071
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002242192 SCV001531583 benign Ehlers-Danlos syndrome, classic type, 1 2024-07-08 criteria provided, single submitter clinical testing
GeneDx RCV003442855 SCV004168805 uncertain significance not provided 2023-04-17 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not located in the triple helical region, where the majority of pathogenic missense variants occur (Symoens et al., 2012; HGMD); Has not been previously published as pathogenic or benign to our knowledge
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004587129 SCV005077061 likely benign not specified 2024-04-22 criteria provided, single submitter clinical testing Variant summary: COL5A1 c.5294G>A (p.Arg1765His) results in a non-conservative amino acid change located in the C-terminal domain (IPR000885) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.6e-05 in 1606866 control chromosomes, predominantly at a frequency of 0.00018 within the South Asian subpopulation in the gnomAD database (v4.1 dataset). The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 5.8-fold of the estimated maximal expected allele frequency for a pathogenic variant in COL5A1 causing Ehlers-Danlos Syndrome phenotype (3.1e-05), strongly suggesting that the variant is a benign polymorphism. To our knowledge, no occurrence of c.5294G>A in individuals affected with Ehlers-Danlos Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 1035130). Based on the evidence outlined above, the variant was classified as likely benign.
Breakthrough Genomics, Breakthrough Genomics RCV003442855 SCV005190576 uncertain significance not provided criteria provided, single submitter not provided

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.