Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV001002279 | SCV001160160 | uncertain significance | Ehlers-Danlos syndrome, kyphoscoliotic type 1 | 2018-12-15 | criteria provided, single submitter | clinical testing | The PLOD1 c.677T>C; p.Val226Ala variant (rs376643174), to our knowledge, is not reported in the medical literature or gene specific databases. This variant is found on two chromosomes in the Genome Aggregation Database, indicating it is not a common polymorphism. The valine at codon 226 is highly conserved, but computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. However, given the lack of clinical and functional data, the significance of the p.Val226Ala variant is uncertain at this time. |
| Invitae | RCV001002279 | SCV001210239 | uncertain significance | Ehlers-Danlos syndrome, kyphoscoliotic type 1 | 2022-08-09 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 226 of the PLOD1 protein (p.Val226Ala). This variant is present in population databases (rs376643174, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with PLOD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 811853). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. |