ClinVar Miner

Submissions for variant NM_000090.3(COL3A1):c.2959G>A (p.Gly987Ser) (rs587779583)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000243223 SCV000319284 pathogenic Cardiovascular phenotype 2019-04-11 criteria provided, single submitter clinical testing Insufficient or conflicting evidence;In silico models in agreement (deleterious) and/or completely conserved position in appropriate species;Rarity in general population databases (dbsnp, esp, 1000 genomes);Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation;Structural Evidence
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne RCV000087534 SCV000966168 pathogenic Ehlers-Danlos syndrome, type 4 2018-10-19 criteria provided, single submitter clinical testing
Invitae RCV000087534 SCV001225507 pathogenic Ehlers-Danlos syndrome, type 4 2019-05-03 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 987 of the COL3A1 protein (p.Gly987Ser). The glycine residue is moderately conserved and there is a small physicochemical difference between glycine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in an individual affected with clinical features of Ehlers-Danlos syndrome (PMID: 29778910) and has been observed in other individuals affected with this syndrome (PMID: 24922459, 25758994). ClinVar contains an entry for this variant (Variation ID: 101296). Glycine residues within the Gly-Xaa-Yaa repeats of the triple helix domain are required for the structure and stability of fibrillar collagens (PMID: 7695699, 8218237, 19344236). In COL3A1, variants that affect these glycine residues are significantly enriched in individuals with disease (PMID: 24922459, 25758994) compared to the general population (ExAC). This variant disrupts the p.Gly987 amino acid residue in COL3A1. Other variant(s) that disrupt this residue have been observed in individuals with COL3A1-related conditions (PMID: 25758994), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Collagen Diagnostic Laboratory,University of Washington RCV000087534 SCV000120421 pathogenic Ehlers-Danlos syndrome, type 4 no assertion criteria provided clinical testing

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