Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| New York Genome Center | RCV003228667 | SCV003925394 | likely pathogenic | Ehlers-Danlos syndrome, type 4 | 2022-01-28 | criteria provided, single submitter | clinical testing | The c.396del (p.Gly133ValfsTer32) variant identified in the COL3A1 gene is the deletion of a single nucleotide resulting in a frameshift at amino acid133/1466 (exon 4/51), and is predicted to incorporate a premature termination codon at approximately 32 amino acids downstream. This is predicted to result in either loss-of-function via nonsense mediated decay or protein truncation. This variant is absent from gnomAD(v3.1.1) suggesting it is not a common benign variant in the populations represented in that database. This variant is absent from ClinVar and to our current knowledge has not been reported in affected individuals in the literature. Multiple loss-of-function variants that are upstream to the c.396del variant have been reported in affected individuals in the literature, and studies show that variants that produced premature termination codons have reduced penetrance, life span extended, and age of first complication delayed compared with missenseand splicing variants [PMID: 21637106, 31075413, 20301667]. Based on the available evidence the c.396del (p.Gly133ValfsTer32) variant is reported as Likely Pathogenic. |