Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001889055 | SCV002155918 | uncertain significance | Ehlers-Danlos syndrome, musculocontractural type | 2021-03-22 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The proline amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with CHST14-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change replaces alanine with proline at codon 15 of the CHST14 protein (p.Ala15Pro). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and proline. |
| Ambry Genetics | RCV002331402 | SCV002633332 | uncertain significance | Cardiovascular phenotype | 2020-09-18 | criteria provided, single submitter | clinical testing | The p.A15P variant (also known as c.43G>C), located in coding exon 1 of the CHST14 gene, results from a G to C substitution at nucleotide position 43. The alanine at codon 15 is replaced by proline, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |