Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000489156 | SCV000577578 | pathogenic | not provided | 2017-09-01 | criteria provided, single submitter | clinical testing | The c.555delT pathogenic variant in the COL3A1 gene has previously been reported in one individual with soft, velvety, translucent skin with atrophic scars, as well as multiple dissections involving the splenic and hepatic branches of the celiac artery and both renal arteries (Schwarze et al., 2001; Leistritz et al., 2011). This variant causes a shift in reading frame starting at codon glycine 186, changing it to a valine, and creating a premature stop codon at position 36 of the new reading frame, denoted p.Gly186ValfsX36. Moreover, mRNA studies demonstrated that c.555delT leads to the incorporation of a premature termination codon resulting in an unstable mRNA product that is rapidly degraded (Schwarze et al., 2001). Other downstream frameshift variants in the COL3A1 gene have been reported in HGMD in association with EDS type IV (Stenson et al., 2014), indicating that loss of function is a mechanism of disease for this gene. Furthermore, the c.555delT variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). |
Johns Hopkins Genomics, |
RCV000087378 | SCV001371778 | pathogenic | Ehlers-Danlos syndrome, type 4 | 2020-01-02 | criteria provided, single submitter | clinical testing | |
Collagen Diagnostic Laboratory, |
RCV000087378 | SCV000120260 | pathogenic | Ehlers-Danlos syndrome, type 4 | no assertion criteria provided | clinical testing | ||
Genome Diagnostics Laboratory, |
RCV000489156 | SCV001807755 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000489156 | SCV001968535 | pathogenic | not provided | no assertion criteria provided | clinical testing |