Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000599604 | SCV000710350 | uncertain significance | not specified | 2018-01-17 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the COL3A1 gene. The c.3213_3221dupCCCTGCTGG variant has not been published as pathogenic or been reported as benign to our knowledge. This variant results in a in-frame duplication of three amino acid residues occuring within a Gly-X-Y motif in the triple helical region of the COL3A1 gene, beginning at codon proline 1072 and ending at codon glycine 1074. Other in-frame duplications in the COL3A1 gene have been reported in Human Gene Mutation Database in association with vEDS (Stenson et al., 2014). Furthermore, the c.3213_3221dupCCCTGCTGG variant has not been observed in large population cohorts (Lek et al., 2016). Nevertheless, this variant lacks observation in a significant number of affected individuals, segregation data, and functional evidence, which would further clarify its pathogenicity. |
Labcorp Genetics |
RCV002532691 | SCV003006318 | uncertain significance | Ehlers-Danlos syndrome, type 4 | 2023-11-11 | criteria provided, single submitter | clinical testing | This variant, c.3213_3221dup, results in the insertion of 3 amino acid(s) of the COL3A1 protein (p.Pro1072_Gly1074dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs771791598, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with COL3A1-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |