ClinVar Miner

Submissions for variant NM_000090.3(COL3A1):c.2805T>C (p.Pro935=) (rs111567071)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000124412 SCV000167845 benign not specified 2014-06-09 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.
Illumina Clinical Services Laboratory,Illumina RCV000313108 SCV000425534 benign Ehlers-Danlos syndrome, type 4 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Invitae RCV000313108 SCV000631652 likely benign Ehlers-Danlos syndrome, type 4 2019-12-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000620608 SCV000738543 likely benign Cardiovascular phenotype 2017-03-13 criteria provided, single submitter clinical testing Synonymous alterations with insufficient evidence to classify as benign;Subpopulation frequency in support of benign classification;In silico models in agreement (benign)
Center for Human Genetics, Inc,Center for Human Genetics, Inc RCV000659423 SCV000781237 likely benign Connective tissue disease 2016-11-01 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000755958 SCV000883643 likely benign not provided 2017-07-30 criteria provided, single submitter clinical testing
Color RCV000777801 SCV000913793 benign Familial thoracic aortic aneurysm and aortic dissection 2018-10-15 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000124412 SCV001372394 benign not specified 2020-06-29 criteria provided, single submitter clinical testing Variant summary: COL3A1 c.2805T>C alters a non-conserved nucleotide resulting in a synonymous change. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00012 in 250242 control chromosomes (gnomAD). The observed variant frequency is approximately 93 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.2805T>C in individuals affected with Aortopathy and no experimental evidence demonstrating its impact on protein function have been reported. Six ClinVar submitters (evaluation after 2014) cite the variant as benign (2x) and likely benign (4x). Based on the evidence outlined above, the variant was classified as benign.

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