ClinVar Miner

Submissions for variant NM_000090.3(COL3A1):c.812G>A (p.Arg271Gln) (rs112185887)

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Total submissions: 18
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000514955 SCV000233349 likely benign not provided 2021-03-24 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 27153395, 21086191, 25637381, 25525159, 24055113, 25758994, 26017485, 26332594, 25834947, 25985138, 25504618, 30122538, 28567303)
Invitae RCV000148458 SCV000283468 likely benign Ehlers-Danlos syndrome, type 4 2020-12-06 criteria provided, single submitter clinical testing
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia RCV000148458 SCV000296869 benign Ehlers-Danlos syndrome, type 4 2015-11-08 criteria provided, single submitter clinical testing
Ambry Genetics RCV000253152 SCV000317901 likely benign Cardiovascular phenotype 2019-02-08 criteria provided, single submitter clinical testing In silico models in agreement (benign);Subpopulation frequency in support of benign classification
Illumina Clinical Services Laboratory,Illumina RCV000148458 SCV000425505 likely benign Ehlers-Danlos syndrome, type 4 2018-03-15 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001283044 SCV000603146 benign none provided 2020-01-31 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000514955 SCV000610622 likely benign not provided 2017-03-10 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000181073 SCV000695380 benign not specified 2019-04-01 criteria provided, single submitter clinical testing Variant summary: COL3A1 c.812G>A (p.Arg271Gln) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0014 in 278388 control chromosomes, predominantly at a frequency of 0.0024 within the Non-Finnish European subpopulation in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 1920 fold of the estimated maximal expected allele frequency for a pathogenic variant in COL3A1 causing Aortopathy phenotype (1.3e-06), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. The variant has been reported in patients with traumatic subarachnoid hemorrhage, familial abdominal aortic aneurysm and in two patients with clinical features of EhlersDanlos syndrome (Pickup _2011, van de Luijtgaarden_2015, Frank_2015). These reports however, do not provide unequivocal conclusions about association of the variant with Aortopathy. In a recent study examining a cohort of cases received to interpret variants originally identified by an outside laboratory, this variant was reportedly identified with another (identity not provided) mutation in 5 out of 14 unrelated probands, was inherited from an unaffected parent in one case and was reportedly found to have a normal type III collagen analysis in one patient (Pepin_2015). To our knowledge, no other experimental evidence demonstrating an impact on protein function has been reported. Nine clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign (X2)/likely benign (X7). Based on the evidence outlined above, the variant was classified as benign.
Center for Human Genetics, Inc,Center for Human Genetics, Inc RCV000680499 SCV000807882 likely benign Connective tissue disease 2018-06-01 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000181073 SCV000854894 likely benign not specified 2017-08-02 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000769564 SCV000900961 likely benign Familial thoracic aortic aneurysm and aortic dissection 2016-06-23 criteria provided, single submitter clinical testing
Color Health, Inc RCV000769564 SCV000910959 likely benign Familial thoracic aortic aneurysm and aortic dissection 2018-03-14 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000514955 SCV001371402 likely benign not provided 2021-03-01 criteria provided, single submitter clinical testing
CSER _CC_NCGL, University of Washington RCV000148458 SCV000190157 likely benign Ehlers-Danlos syndrome, type 4 2014-06-01 no assertion criteria provided research
GenomeConnect, ClinGen RCV000148458 SCV000606896 not provided Ehlers-Danlos syndrome, type 4 no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000514955 SCV001797897 likely benign not provided no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000514955 SCV001808298 likely benign not provided no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000514955 SCV001929962 likely benign not provided no assertion criteria provided clinical testing

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