ClinVar Miner

Submissions for variant NM_001278074.1(COL5A1):c.739G>A (p.Ala247Thr) (rs769115550)

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
Illumina Clinical Services Laboratory,Illumina RCV000284861 SCV000478509 uncertain significance Ehlers-Danlos syndrome, type 7A 2016-06-14 criteria provided, single submitter clinical testing
GeneDx RCV000481421 SCV000569080 uncertain significance not provided 2018-05-15 criteria provided, single submitter clinical testing The A247T variant of uncertain significance in the COL5A1 gene has not been reported previously as a pathogenic variant or benign variant, to our knowledge. This variant is observed in 0.0047% (6/126706) of alleles from individuals of European (non-Finnish) ancestry in large population cohorts (Lek et al., 2016). In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Furthermore, the A247T variant does not affect a Glycine residue in a Gly-X-Y motif in the triple helical region of the COL5A1 gene, where the majority of pathogenic missense variants occur (Stenson et al., 2014). However, the A247T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign.
Ambry Genetics RCV000618500 SCV000738659 uncertain significance Cardiovascular phenotype 2017-02-16 criteria provided, single submitter clinical testing Insufficient evidence
Invitae RCV001046554 SCV001210459 uncertain significance Ehlers-Danlos syndrome, classic type 2019-05-31 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 247 of the COL5A1 protein (p.Ala247Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs769115550, ExAC 0.003%). This variant has not been reported in the literature in individuals with COL5A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 365707). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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.