ClinVar Miner

Submissions for variant NM_000093.5(COL5A1):c.4765G>A (p.Ala1589Thr)

gnomAD frequency: 0.00001  dbSNP: rs377138881
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000195865 SCV000249847 uncertain significance not provided 2024-10-30 criteria provided, single submitter clinical testing In silico analysis indicates that this missense variant does not alter protein structure/function; Not located in the triple helical region, where the majority of pathogenic missense variants occur (PMID: 22696272; HGMD); This variant is associated with the following publications: (PMID: 32906206, 22696272, 29924831)
Labcorp Genetics (formerly Invitae), Labcorp RCV002229061 SCV000959698 likely benign Ehlers-Danlos syndrome, classic type, 1 2023-07-07 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001199934 SCV001370719 uncertain significance not specified 2020-05-18 criteria provided, single submitter clinical testing Variant summary: COL5A1 c.4765G>A (p.Ala1589Thr) results in a non-conservative amino acid change in 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 3.6e-05 in 251682 control chromosomes (gnomAD and publication). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.4765G>A has been reported in the literature in one individual affected with keratoconus (Lucas_2018). The report does not provide unequivocal conclusions about association of the variant with Ehlers-Danlos Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One ClinVar submitter (evaluation after 2014) cites the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Ambry Genetics RCV002336524 SCV002634691 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2021-03-02 criteria provided, single submitter clinical testing The c.4765G>A (p.A1589T) alteration is located in exon 62 (coding exon 62) of the COL5A1 gene. This alteration results from a G to A substitution at nucleotide position 4765, causing the alanine (A) at amino acid position 1589 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV005042417 SCV005678132 uncertain significance Ehlers-Danlos syndrome, classic type, 1; Fibromuscular dysplasia, multifocal 2024-06-18 criteria provided, single submitter clinical testing

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.