Submissions for variant NM_000093.5(COL5A1):c.4122G>A (p.Thr1374=)

gnomAD frequency: 0.14130  dbSNP: rs3827848

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000124448	SCV000167881	benign	not specified	2012-11-13	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.
PreventionGenetics, part of Exact Sciences	RCV000124448	SCV000302207	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000315775	SCV000478567	likely benign	Ehlers-Danlos syndrome type 7A	2016-06-14	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000587906	SCV000603164	benign	not provided	2023-11-29	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587906	SCV000695395	benign	not provided	2017-03-10	criteria provided, single submitter	clinical testing	Variant summary: The COL5A1 c.4122G>A (p.Thr1374Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a polymorphism outcome for this variant. 5/5 splice prediction tools predict weakening the canonical donor cite. However, these predictions have yet to be confirmed by functional studies. This variant was found in 17922/121286 control chromosomes (1465 homozygotes) at a frequency of 0.1477664, which is approximately 118213 times the estimated maximal expected allele frequency of a pathogenic COL5A1 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	RCV002312838	SCV000738285	benign	Familial thoracic aortic aneurysm and aortic dissection	2015-02-04	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001517576	SCV001726099	benign	Ehlers-Danlos syndrome, classic type, 1	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001517576	SCV002554594	benign	Ehlers-Danlos syndrome, classic type, 1	2022-03-15	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002269892	SCV002554595	benign	Fibromuscular dysplasia, multifocal	2022-03-15	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000587906	SCV005226592	likely benign	not provided		criteria provided, single submitter	not provided
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000124448	SCV001740676	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000124448	SCV001807829	benign	not specified		no assertion criteria provided	clinical testing