Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002235045 | SCV000955332 | likely pathogenic | Ehlers-Danlos syndrome, classic type, 1 | 2018-12-05 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with asparagine at codon 1735 of the COL5A1 protein (p.Ser1735Asn). The serine residue is moderately conserved and there is a small physicochemical difference between serine and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in an individual with clinical features of Ehlers-Danlos syndrome (Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
Gene |
RCV001759582 | SCV002006063 | likely pathogenic | not provided | 2023-03-10 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Ce |
RCV001759582 | SCV002821986 | uncertain significance | not provided | 2022-12-01 | criteria provided, single submitter | clinical testing | COL5A1: PM2 |
Illumina Laboratory Services, |
RCV002235045 | SCV004036005 | uncertain significance | Ehlers-Danlos syndrome, classic type, 1 | 2023-04-13 | criteria provided, single submitter | clinical testing | The COL5A1 c.5204G>A (p.Ser1735Asn) missense variant has not, to our knowledge, been reported in the peer-reviewed literature. This variant is not observed in version 2.1.1 or version 3.1.2 of the Genome Aggregation Database. Multiple lines of computational evidence suggest the variant may impact the gene or gene product. Based on the available evidence, the c.5204G>A (p.Ser1735Asn) variant is classified as a variant of uncertain significance for classic Ehlers-Danlos syndrome. |