Submissions for variant NM_000393.5(COL5A2):c.851C>T (p.Pro284Leu)

gnomAD frequency: 0.00004  dbSNP: rs540573303

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000259606	SCV000425662	uncertain significance	Ehlers-Danlos syndrome type 7A	2016-06-14	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002314060	SCV000738726	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2022-02-17	criteria provided, single submitter	clinical testing	The c.851C>T (p.P284L) alteration is located in exon 12 (coding exon 12) of the COL5A2 gene. This alteration results from a C to T substitution at nucleotide position 851, causing the proline (P) at amino acid position 284 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002229964	SCV001131946	likely benign	Ehlers-Danlos syndrome, classic type, 1	2023-12-12	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001142042	SCV001302439	likely benign	Ehlers-Danlos syndrome, classic type, 2	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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
GeneDx	RCV001731613	SCV001983167	uncertain significance	not provided	2021-09-24	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Reported in ClinVar (ClinVar Variant ID# 333147; Landrum et al., 2016)
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001142042	SCV002049236	likely benign	Ehlers-Danlos syndrome, classic type, 2	2021-07-21	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002278513	SCV002565852	uncertain significance	Ehlers-Danlos syndrome	2020-04-01	criteria provided, single submitter	clinical testing