Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000806079 | SCV000946060 | pathogenic | Ehlers-Danlos syndrome, type 4 | 2018-10-10 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with COL3A1-related disease. This variant is present in population databases (rs772827388, ExAC 0.009%). This sequence change creates a premature translational stop signal (p.Pro314Phefs*97) in the COL3A1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in COL3A1 are known to be pathogenic (PMID: 24922459). For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001824888 | SCV002074385 | likely pathogenic | Familial aortopathy | 2022-01-21 | criteria provided, single submitter | clinical testing | Variant summary: COL3A1 c.937_938dupCT (p.Pro314PhefsX97) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 4e-06 in 251342 control chromosomes (gnomAD). To our knowledge, no occurrence of c.937_938dupCT in individuals affected with Aortopathy and no experimental evidence demonstrating its impact on protein function have been reported. A ClinVar submitter (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |