Submissions for variant NM_000088.4(COL1A1):c.3076C>T (p.Arg1026Ter)

dbSNP: rs72653173

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000029575	SCV000052227	pathogenic	Osteogenesis imperfecta	2011-08-18	criteria provided, single submitter	curation	Converted during submission to Pathogenic.
GeneDx	RCV000498745	SCV000589582	pathogenic	not provided	2024-12-26	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 26627451, 36709916, 37079061, 37334733, 37270749, 35909573, 34902613, 36951356, 29499418, 28396251, 15024745, 17392686, 23682531, 27044453, 22753364, 24767406, 15241796, 31447884, 30692697, 30715774, 32770541, 34358384, 32166892, 37810882, 38807347, 11113887, 21667357)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000551341	SCV000627224	pathogenic	Osteogenesis imperfecta type I	2024-09-29	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg1026*) in the COL1A1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in COL1A1 are known to be pathogenic (PMID: 7942841, 9295084, 9443882). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with osteogenesis imperfecta, type 1 (PMID: 11113887, 27044453). ClinVar contains an entry for this variant (Variation ID: 35920). For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen	RCV000498745	SCV001246758	pathogenic	not provided	2023-10-01	criteria provided, single submitter	clinical testing	COL1A1: PVS1, PM2, PS4:Moderate
Kariminejad - Najmabadi Pathology & Genetics Center	RCV001814012	SCV001755295	pathogenic	Abnormality of the skeletal system	2021-07-10	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000498745	SCV001880358	pathogenic	not provided	2021-04-27	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). This variant appears to segregate with disease in at least one family. In some published literature, this variant is referred to as R848X.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV000029575	SCV002564718	pathogenic	Osteogenesis imperfecta	2018-08-01	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002504826	SCV002798099	pathogenic	Osteogenesis imperfecta with normal sclerae, dominant form; Osteogenesis imperfecta, perinatal lethal; Osteogenesis imperfecta type III; Infantile cortical hyperostosis; Ehlers-Danlos syndrome, arthrochalasia type; Osteogenesis imperfecta type I; Osteoporosis; Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 1	2022-05-05	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000498745	SCV003800551	pathogenic	not provided	2022-03-21	criteria provided, single submitter	clinical testing	The COL1A1 c.3076C>T; p.Arg1026Ter variant (rs72653173), also known as p.Arg848Ter, is reported in the literature in multiple individuals and families affected with osteogenesis imperfecta type1 (Duan 2016, Ries 2000, Ries-Levavi 2004). This variant is reported in ClinVar (Variation ID: 35920) and is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. References: Duan H et al. Identification of two recurrent mutations of COL1A1 gene in Chinese Van der Hoeve syndrome patients. Acta Otolaryngol. 2016 Aug;136(8):786-91. PMID: 27044453. Ries L et al. Prenatal diagnosis of a novel COL1A1 mutation in osteogenesis imperfecta type I carried through full term pregnancy. Prenat Diagn. 2000 Nov;20(11):876-80. PMID: 11113887. Ries-Levavi L et al. Genetic and biochemical analyses of Israeli osteogenesis imperfecta patients. Hum Mutat. 2004 Apr;23(4):399-400. PMID: 15024745.
Baylor Genetics	RCV000029575	SCV000854598	pathogenic	Osteogenesis imperfecta	2018-11-18	no assertion criteria provided	clinical testing
GenomeConnect - Invitae Patient Insights Network	RCV001535575	SCV001749564	not provided	Infantile cortical hyperostosis; Ehlers-Danlos syndrome, arthrochalasia type; Osteogenesis imperfecta		no assertion provided	phenotyping only	Variant interpreted as Pathogenic and reported on 06-26-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.
PreventionGenetics, part of Exact Sciences	RCV004737165	SCV005366204	pathogenic	COL1A1-related disorder	2024-09-27	no assertion criteria provided	clinical testing	The COL1A1 c.3076C>T variant is predicted to result in premature protein termination (p.Arg1026*). This variant has been reported in multiple unrelated individuals with osteogenesis imperfecta type 1 (for example, see : Ries-Levavi et al. 2004. PubMed ID: 15024745; Hartikka et al. 2004. PubMed ID: 15241796; Table S1, Li et al. 2019. PubMed ID: 30715774). This variant has not been reported in a large population database, indicating this variant is rare. Nonsense variants in COL1A1 are expected to be pathogenic. This variant is interpreted as pathogenic.