Submissions for variant NM_000093.5(COL5A1):c.5270C>T (p.Thr1757Met)

gnomAD frequency: 0.00346  dbSNP: rs2229817

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000124473	SCV000167906	benign	not specified	2013-01-23	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	RCV000124473	SCV000302242	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000407995	SCV000478594	likely benign	Ehlers-Danlos syndrome type 7A	2016-06-14	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001507183	SCV000560001	benign	Ehlers-Danlos syndrome, classic type, 1	2025-02-04	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000586099	SCV000603178	benign	not provided	2024-10-16	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586099	SCV000695391	benign	not provided	2017-03-15	criteria provided, single submitter	clinical testing	Variant summary: The COL5A1 c.5270C>T (p.Thr1757Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. 4/5 in silico tools predict a damaging outcome for this variant. This variant was found in 1444/119592 control chromosomes (24 homozygotes) at a frequency of 0.0120744, which is approximately 9660 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/likely benign. Taken together, based on the prevalence in general population this variant is classified as benign.
Ambry Genetics	RCV002312845	SCV000738365	benign	Familial thoracic aortic aneurysm and aortic dissection	2015-06-23	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.
Illumina Laboratory Services, Illumina	RCV000466128	SCV001330725	benign	Ehlers-Danlos syndrome, classic type	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.
Genome-Nilou Lab	RCV001507183	SCV002554691	benign	Ehlers-Danlos syndrome, classic type, 1	2022-03-15	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002269914	SCV002554693	benign	Fibromuscular dysplasia, multifocal	2022-03-15	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002277221	SCV002565778	benign	Ehlers-Danlos syndrome	2022-07-16	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000586099	SCV005228553	likely benign	not provided		criteria provided, single submitter	not provided
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000124473	SCV001808274	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000124473	SCV001930743	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000124473	SCV001970631	benign	not specified		no assertion criteria provided	clinical testing