Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Human Genome Sequencing Center Clinical Lab, |
RCV004556985 | SCV005045744 | likely pathogenic | Ehlers-Danlos syndrome, type 4 | 2023-11-02 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV004556985 | SCV005427305 | likely pathogenic | Ehlers-Danlos syndrome, type 4 | 2024-03-28 | criteria provided, single submitter | clinical testing | The c.1694_1697del (p.Pro565Leufs*225) variant in COL3A1 gene, that encodes for collagen type III alpha 1 chain, creates a premature termination codon that is predicted to lead to absent or truncated protein product. This variant has not been reported in the literature for COL3A1-related conditions. Loss-of-function variants in COL3A1 gene are well known to be pathogenic and ClinGen score shows sufficient evidence of haploinsufficiency of this gene (PMID: 11577371, 24922459, 24650746). Loss-of-function variants downstream of this variant are reported to be pathogenic in the literature (PMID: 30474650, 31141158, 22019127, 29381997, 30474650) and in ClinVar (ClinVar ID:2418894, 1458343). This variant is absent in the general population database, gnomAD. Therefore, the c.1694_1697del (p.Pro565Leufs*225) variant in the COL3A1 gene is classified as likely pathogenic. |