ClinVar Miner

Submissions for variant NM_000090.4(COL3A1):c.505C>T (p.Leu169Phe)

gnomAD frequency: 0.00061  dbSNP: rs111391222
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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CSER _CC_NCGL, University of Washington RCV000148459 SCV000190158 uncertain significance Aortic aneurysm 2014-06-01 criteria provided, single submitter research Low GERP score may suggest that this variant may belong in a lower pathogenicity class
GeneDx RCV000181067 SCV000233343 benign not specified 2018-02-22 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics RCV000771255 SCV000317906 benign Familial thoracic aortic aneurysm and aortic dissection 2015-06-20 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Illumina Laboratory Services, Illumina RCV000325556 SCV000425500 likely benign Ehlers-Danlos syndrome, type 4 2018-04-26 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). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Labcorp Genetics (formerly Invitae), Labcorp RCV000325556 SCV000554693 likely benign Ehlers-Danlos syndrome, type 4 2024-01-31 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000771255 SCV000903364 benign Familial thoracic aortic aneurysm and aortic dissection 2018-04-07 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV000771255 SCV001333507 benign Familial thoracic aortic aneurysm and aortic dissection 2018-06-14 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV002277293 SCV002565649 likely benign Ehlers-Danlos syndrome 2020-01-01 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000181067 SCV004121981 likely benign not specified 2023-10-23 criteria provided, single submitter clinical testing Variant summary: COL3A1 c.505C>T (p.Leu169Phe) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0008 in 251010 control chromosomes. The observed variant frequency is approximately 640 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 benign. To our knowledge, no occurrence of c.505C>T in individuals affected with Aortopathy and no experimental evidence demonstrating its impact on protein function have been reported. Eight submitters have cited clinical-significance assessments for this variant to ClinVar after 2014 and classified as benign/likely benign (n=7) and VUS (n=1). Based on the evidence outlined above, the variant was classified as likely benign.
CeGaT Center for Human Genetics Tuebingen RCV003430712 SCV004148274 benign not provided 2024-11-01 criteria provided, single submitter clinical testing COL3A1: BS1, BS2
Knight Diagnostic Laboratories, Oregon Health and Sciences University RCV000325556 SCV000493726 uncertain significance Ehlers-Danlos syndrome, type 4 2015-09-01 no assertion criteria provided clinical testing

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