ClinVar Miner

Submissions for variant NM_000088.3(COL1A1):c.1243C>T (p.Arg415Ter) (rs72648326)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000516899 SCV000612892 pathogenic not provided 2017-06-21 criteria provided, single submitter clinical testing
Invitae RCV000490754 SCV000627165 pathogenic Osteogenesis imperfecta type I 2019-11-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg415*) in the COL1A1 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 been reported in the literature in individuals affected with osteogenesis imperfecta, type 1 (PMID: 8808594, 8613526, 25944380, 27132807, 15024745). ClinVar contains an entry for this variant (Variation ID: 425597). Loss-of-function variants in COL1A1 are known to be pathogenic (PMID: 7942841, 9295084, 9443882). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics,Fulgent Genetics RCV000763412 SCV000894141 pathogenic Osteogenesis imperfecta with normal sclerae, dominant form; Postmenopausal osteoporosis; Osteogenesis imperfecta, recessive perinatal lethal; Osteogenesis imperfecta type III; Infantile cortical hyperostosis; Ehlers-Danlos syndrome, procollagen proteinase deficient; Osteogenesis imperfecta type I 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000516899 SCV001168430 pathogenic not provided 2019-03-11 criteria provided, single submitter clinical testing The R415X nonsense variant has been reported previously in association with osteogenesis imperfecta (Willing et al., 1996; Zhang et al., 2016). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. R415X has been shown to lead to lower levels of R415X-mRNA compared to wild-type (Willing et al., 1996). The variant is not observed in large population cohorts (Lek et al., 2016). We interpret this variant as pathogenic.
Department of Medical Sciences,Uppsala University RCV000490754 SCV000574589 pathogenic Osteogenesis imperfecta type I no assertion criteria provided clinical testing

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