Submissions for variant NM_000093.5(COL5A1):c.4370C>T (p.Pro1457Leu)

gnomAD frequency: 0.00001  dbSNP: rs201875250

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000288001	SCV000478575	uncertain significance	Ehlers-Danlos syndrome type 7A	2016-06-14	criteria provided, single submitter	clinical testing
GeneDx	RCV000519661	SCV000619368	uncertain significance	not provided	2024-08-15	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Occurs in the triple helical domain at the X position in the canonical Gly-X-Y repeat; although this variant may have an effect on normal protein folding and function, missense substitution at the X position is not a common mechanism of disease (PMID: 22696272; HGMD); Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 22696272)
Illumina Laboratory Services, Illumina	RCV001168078	SCV001330642	likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002230724	SCV001486854	benign	Ehlers-Danlos syndrome, classic type, 1	2023-10-26	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002278631	SCV002565748	uncertain significance	Ehlers-Danlos syndrome	2021-03-24	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004022111	SCV005032203	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2024-02-13	criteria provided, single submitter	clinical testing	The p.P1457L variant (also known as c.4370C>T), located in coding exon 56 of the COL5A1 gene, results from a C to T substitution at nucleotide position 4370. The proline at codon 1457 is replaced by leucine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear.