Submissions for variant NM_000090.4(COL3A1):c.1927T>C (p.Leu643=)

gnomAD frequency: 0.00244  dbSNP: rs41263757

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000124406	SCV000167839	benign	not specified	2013-05-09	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000229097	SCV000283456	benign	Ehlers-Danlos syndrome, type 4	2025-01-27	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000124406	SCV000302026	benign	not specified		criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000124406	SCV000339657	benign	not specified	2016-02-26	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000229097	SCV000425521	benign	Ehlers-Danlos syndrome, type 4	2018-01-13	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000588600	SCV000695361	benign	not provided	2017-02-06	criteria provided, single submitter	clinical testing	Variant summary: The COL3A1 c.1927T>C (p.Leu643Leu) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may create a novel ESE site of SF2/ASF. However, these predictions have yet to be confirmed by functional studies. This variant was found in 284/116860 control chromosomes (2 homozygotes) at a frequency of 0.0024303, which is approximately 1944 times the estimated maximal expected allele frequency of a pathogenic COL3A1 variant (0.0000013), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. Taken together, this variant is classified as benign.
Ambry Genetics	RCV000771147	SCV000738438	benign	Familial thoracic aortic aneurysm and aortic dissection	2016-01-12	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000588600	SCV000885230	benign	not provided	2023-03-02	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000771147	SCV000902960	benign	Familial thoracic aortic aneurysm and aortic dissection	2018-03-14	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000588600	SCV001501788	likely benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	COL3A1: BP4, BP7
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002277192	SCV002565614	benign	Ehlers-Danlos syndrome	2021-07-26	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000771147	SCV004240462	benign	Familial thoracic aortic aneurysm and aortic dissection	2023-03-10	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000124406	SCV001808926	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000588600	SCV001966604	likely benign	not provided		no assertion criteria provided	clinical testing