ClinVar Miner

Submissions for variant NM_000090.3(COL3A1):c.4087C>T (p.Arg1363Ter) (rs794728060)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181123 SCV000233399 pathogenic not provided 2016-08-10 criteria provided, single submitter clinical testing TheR1363X variant in the COL3A1 gene has not been reported previously as a disease-causing variant nor as a benign polymorphism, to our knowledge. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R1363X variant was not observed in approximately 6,500 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 R1363X variant is interpreted as a disease-causing variant
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine RCV000709719 SCV000839947 likely pathogenic Ehlers-Danlos syndrome, type 4 2017-04-12 criteria provided, single submitter clinical testing The c.4087C>T (p.Arg1363*) variant has not been detected in our patients database nor has been seen in the ExAC population database. However, this variant was reported in Clinvar (submission accession # SCV000233399.7) as pathogenic by Genedx. No patient information was available for this Clinvar entry. This variant is predicted to create a non sense variant and a premature stop codon at amino acid position 1363 of the COL3A1 protein. This variant is thus predicted to result in a loss of function of the protein. Loss of function variants have reduced penetrance compared to missense and splicing variants, and studies have shown that the phenotype seems to be limited almost entirely to vascular events [PMID 21637106]. This variant is thus classified as likely pathogenic.
Invitae RCV000709719 SCV000931283 pathogenic Ehlers-Danlos syndrome, type 4 2018-08-07 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg1363*) in the COL3A1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with COL3A1-related disease. ClinVar contains an entry for this variant (Variation ID: 199753). Loss-of-function variants in COL3A1 are known to be pathogenic (PMID: 24922459). For these reasons, this variant has been classified as Pathogenic.

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