Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000195939 | SCV000249807 | uncertain significance | not provided | 2020-09-25 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); 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 (Symoens et al., 2012; Stenson et al., 2014); Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 212951; Landrum et al., 2016) |
| Labcorp Genetics |
RCV002229044 | SCV000631476 | benign | Ehlers-Danlos syndrome, classic type, 1 | 2025-01-29 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002315543 | SCV000738656 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2021-03-23 | criteria provided, single submitter | clinical testing | The p.P917L variant (also known as c.2750C>T), located in coding exon 34 of the COL5A1 gene, results from a C to T substitution at nucleotide position 2750. The proline at codon 917 is replaced by leucine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| ARUP Laboratories, |
RCV000195939 | SCV002049931 | uncertain significance | not provided | 2021-02-25 | criteria provided, single submitter | clinical testing | The COL5A1 c.2750C>T; p.Pro917Leu variant (rs375600865), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 212951). This variant is found in the general population with an overall allele frequency of 0.002% (5/251216 alleles) in the Genome Aggregation Database. The proline at codon 917 is highly conserved, but computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.682). However, given the lack of clinical and functional data, the significance of the p.Pro917Leu variant is uncertain at this time. |
| Genomic Medicine Center of Excellence, |
RCV002229044 | SCV005375265 | likely benign | Ehlers-Danlos syndrome, classic type, 1 | 2024-10-13 | criteria provided, single submitter | clinical testing | This variant (GRCh38; NM_001278074.1:c.2750C>T:p.Pro917Leu) results in a missense mutation with the conversion of Proline (Basic amino acid) to Leucine (Basic amino acid) in the COL5A1 protein. Observed in healthy adults individual for a dominant disorder Missense variant in a gene for which primarily truncating variants are known to cause disease. Lack of segregation in affected family members (internal) A literature search was performed for the gene and associated variants. Based on this search no publications were found. In summary, this variant meets our criteria for classification as Benign based on the evidence outlined. |
| Mayo Clinic Laboratories, |
RCV000195939 | SCV005410904 | uncertain significance | not provided | 2024-01-19 | criteria provided, single submitter | clinical testing | |
| Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, |
RCV005404374 | SCV006068990 | uncertain significance | Cardiovascular phenotype | 2025-04-09 | criteria provided, single submitter | clinical testing | PP3 |