Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clinical Genomics Laboratory, |
RCV001253763 | SCV001427067 | likely pathogenic | Ehlers-Danlos syndrome, type 4 | 2019-08-06 | no assertion criteria provided | clinical testing | The p.Glu397* variant in the COL3A1 gene has not been previously reported in association with disease. This variant was absent from large population databases, including the Genome Aggregation Database (http://gnomad.broadinstitute.org/). The p.Glu397* variant leads to a premature stop codon in exon 17 of 51 coding exons, and is therefore predicted to undergo nonsense-mediated decay resulting in a truncated or absent protein. Heterozygous loss of function is an established mechanism of disease for the COL3A1 gene. These data were assessed using the ACMG/AMP variant interpretation guidelines. In summary, there is sufficient evidence to classify the p.Glu397* variant as likely pathogenic for vascular Ehlers-Danlos syndrome in an autosomal dominant manner based on the information above. [ACMG evidence codes used: PVS1; PM2] |