Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001705094 | SCV000249799 | uncertain significance | not provided | 2024-05-24 | criteria provided, single submitter | clinical testing | Has not been previously reported as pathogenic or benign in association with cEDS to our knowledge; 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); This variant is associated with the following publications: (PMID: 29924831, 32938213, 36043395, 33161638) |
Labcorp Genetics |
RCV002228843 | SCV000755928 | likely benign | Ehlers-Danlos syndrome, classic type, 1 | 2024-10-12 | criteria provided, single submitter | clinical testing | |
Victorian Clinical Genetics Services, |
RCV002228843 | SCV002767922 | uncertain significance | Ehlers-Danlos syndrome, classic type, 1 | 2022-09-02 | 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). 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 arginine to tryptophan. (I) 0251 - This variant is heterozygous. (I) 0302 - Variant is present in gnomAD <0.001 for a dominant condition (v2 & v3: 28 heterozygotes, 0 homozygotes). (SP) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (v2 & v3: 20 heterozygotes, 0 homozygotes). (I) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0600 - Variant is located in the annotated triple helical domain (DECIPHER). (I) 0710 - Another missense variant comparable to the one identified in this case has inconclusive previous evidence for pathogenicity. p.(Arg611Gln) has been reported as a VUS, including in an individual with suspected aortopathy (ClinVar, VCGS). (I) 0808 - Previous reports of pathogenicity for this variant are conflicting. This variant has been reported as a VUS, including in three affected individuals (ClinVar, VCGS, PMID: 32938213). It has also been reported in an individual with classic Ehlers-Danlos syndrome (PMID: 33161638). However, it has also been reported as likely benign once in ClinVar without further information provided. (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 |
Ce |
RCV001705094 | SCV003917731 | uncertain significance | not provided | 2023-01-01 | criteria provided, single submitter | clinical testing | COL5A1: PP3 |
Ambry Genetics | RCV004609323 | SCV005106040 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2024-04-11 | criteria provided, single submitter | clinical testing | The p.R611W variant (also known as c.1831C>T), located in coding exon 17 of the COL5A1 gene, results from a C to T substitution at nucleotide position 1831. The arginine at codon 611 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |
Genome |
RCV001249369 | SCV001423358 | not provided | Ehlers-Danlos syndrome, classic type, 2; Ehlers-Danlos syndrome, classic type | no assertion provided | phenotyping only | Variant interpretted as Uncertain significance and reported on 07-18-2019 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. |