Submissions for variant NM_000093.5(COL5A1):c.4482G>C (p.Pro1494=)

dbSNP: rs2228560

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000124459	SCV000167892	benign	not specified	2012-11-02	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	RCV000124459	SCV000302223	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000405317	SCV000478580	benign	Ehlers-Danlos syndrome type 7A	2016-06-14	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000590016	SCV000695399	benign	not provided	2017-03-15	criteria provided, single submitter	clinical testing	Variant summary: The COL5A1 c.4482G>C (p.Pro1494Pro) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may eliminate an SC35 ESE site. However, these predictions have yet to be confirmed by functional studies. The variant lies within the collagen triple helix repeat domain of the protein (InterPro). This variant was found in 45450/121210 control chromosomes (8705 homozygotes) at a frequency of 0.3749691, which is approximately 299975 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. The variant has been cited in at least one publication and was described by the authors as a common polymorphism (Symoens_HM_2012). Taken together, this variant is classified as benign.
Ambry Genetics	RCV002312842	SCV000738270	benign	Familial thoracic aortic aneurysm and aortic dissection	2015-01-23	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	RCV001513762	SCV001721437	benign	Ehlers-Danlos syndrome, classic type, 1	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001513762	SCV001876529	benign	Ehlers-Danlos syndrome, classic type, 1	2021-07-30	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001657782	SCV001876540	benign	Fibromuscular dysplasia, multifocal	2021-07-30	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000590016	SCV005321141	benign	not provided		criteria provided, single submitter	not provided
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000124459	SCV001743230	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000124459	SCV001806891	benign	not specified		no assertion criteria provided	clinical testing