Submissions for variant NM_000393.5(COL5A2):c.2741C>T (p.Ala914Val) (rs201486858)

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	RCV000196083	SCV000249953	uncertain significance	not provided	2017-09-06	criteria provided, single submitter	clinical testing	The A914V variant in the COL5A2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The A914V variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The A914V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret A914V as a variant of uncertain significance.
Ambry Genetics	RCV000251071	SCV000319649	uncertain significance	Cardiovascular phenotype	2016-08-09	criteria provided, single submitter	clinical testing	Lines of evidence used in support of classification: Insufficient or conflicting evidence
Illumina Clinical Services Laboratory,Illumina	RCV000396728	SCV000425636	uncertain significance	Ehlers-Danlos syndrome, type 7A	2016-06-14	criteria provided, single submitter	clinical testing
Invitae	RCV000457016	SCV000547884	uncertain significance	Ehlers-Danlos syndrome, classic type	2018-09-06	criteria provided, single submitter	clinical testing	This sequence change replaces alanine with valine at codon 914 of the COL5A2 protein (p.Ala914Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs201486858, ExAC 0.06%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with COL5A2-related disease. ClinVar contains an entry for this variant (Variation ID: 213092). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Fulgent Genetics,Fulgent Genetics	RCV000457016	SCV000895374	uncertain significance	Ehlers-Danlos syndrome, classic type	2018-10-31	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.