Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000198488 | SCV000249791 | uncertain significance | not provided | 2024-01-30 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not located in the triple helical region, where the majority of pathogenic missense variants occur (PMID: 22696272); This variant is associated with the following publications: (PMID: 22696272) |
| Labcorp Genetics |
RCV002228840 | SCV000549009 | benign | Ehlers-Danlos syndrome, classic type, 1 | 2023-06-28 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002315539 | SCV000738653 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2024-02-29 | criteria provided, single submitter | clinical testing | The p.M521V variant (also known as c.1561A>G), located in coding exon 12 of the COL5A1 gene, results from an A to G substitution at nucleotide position 1561. The methionine at codon 521 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly 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. |
| Victorian Clinical Genetics Services, |
RCV002228840 | SCV005086558 | uncertain significance | Ehlers-Danlos syndrome, classic type, 1 | 2023-07-17 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3B. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with classic type Ehlers-Danlos syndrome 1 (MIM#130000) whereas the mechanism of disease for multifocal fibromuscular dysplasia (MIM#619329) is unknown. Dominant negative is a suggested mechanism of disease (PMID: 32720758). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from methionine to valine. (I) 0251 - This variant is heterozygous. (I) 0302 - Variant is present in gnomAD <0.001 for a dominant condition (v2 & v3: 5 heterozygotes, 0 homozygotes). (SP) 0502 - Missense variant with conflicting in silico predictions and high conservation. (I) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0809 - Previous evidence of pathogenicity for this variant is inconclusive. This variant has been reported as a VUS (Clinvar). (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |