Submissions for variant NM_000090.4(COL3A1):c.3537C>A (p.Gly1179=)

gnomAD frequency: 0.00012  dbSNP: rs146837092

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587356	SCV000695372	benign	not provided	2017-07-31	criteria provided, single submitter	clinical testing	Variant summary: The COL3A1 c.3537C>A (p.Gly1179Gly) 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 affect ESE sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 21/121254 control chromosomes at a frequency of 0.0001732, which is approximately 139 times the estimated maximal expected allele frequency of a pathogenic COL3A1 variant (0.0000013), suggesting this variant is likely a benign polymorphism. The variant of interest has not, to our knowledge, been reported in affected individuals via publications. Taken together, this variant is classified as benign.
Color Diagnostics, LLC DBA Color Health	RCV000772487	SCV000905666	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2018-05-11	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001085406	SCV001006701	likely benign	Ehlers-Danlos syndrome, type 4	2025-02-04	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000587356	SCV002063983	likely benign	not provided	2021-12-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000772487	SCV002616171	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2022-06-14	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
All of Us Research Program, National Institutes of Health	RCV001085406	SCV004831828	likely benign	Ehlers-Danlos syndrome, type 4	2024-02-05	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000587356	SCV005262403	likely benign	not provided		criteria provided, single submitter	not provided
PreventionGenetics, part of Exact Sciences	RCV004530636	SCV004725272	likely benign	COL3A1-related disorder	2023-10-03	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).