ClinVar Miner

Submissions for variant NM_000090.4(COL3A1):c.3103G>T (p.Gly1035Cys)

dbSNP: rs587779704
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000087706 SCV000814816 likely pathogenic Ehlers-Danlos syndrome, type 4 2019-01-01 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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, missense variants at these glycine residues are significantly enriched in individuals with disease (PMID: 24922459, 25758994) compared to the general population (ExAC). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has been reported in an individual affected with Ehlers–Danlos syndrome (PMID: 10706896). This variant is also known as G868C in the literature. ClinVar contains an entry for this variant (Variation ID: 101467). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with cysteine at codon 1035 of the COL3A1 protein (p.Gly1035Cys). The glycine residue is moderately conserved and there is a large physicochemical difference between glycine and cysteine.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000781312 SCV000919238 likely pathogenic Familial aortopathy 2017-11-06 criteria provided, single submitter clinical testing Variant summary: The COL3A1 c.3103G>T (p.Gly1035Cys) variant involves the alteration of a conserved nucleotide and a critical amino acid. 4/4 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). This variant is absent in 246170 control chromosomes in gnomAD. This variant was reported in one ED patient and was associated with arterial complications (Pepin_2000). In addition, one clinical diagnostic laboratories classified this variant as pathogenic. Taken together, this variant is classified as likely pathogenic.
Collagen Diagnostic Laboratory, University of Washington RCV000087706 SCV000120599 pathogenic Ehlers-Danlos syndrome, type 4 no assertion criteria provided clinical testing

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