Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001246257 | SCV001419598 | uncertain significance | Ehlers-Danlos syndrome, musculocontractural type | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine with isoleucine at codon 46 of the CHST14 protein (p.Met46Ile). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and isoleucine. 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 variant has not been reported in the literature in individuals affected with CHST14-related conditions. 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. |
| Ambry Genetics | RCV004034857 | SCV005030317 | uncertain significance | Cardiovascular phenotype | 2024-02-16 | criteria provided, single submitter | clinical testing | The p.M46I variant (also known as c.138G>C), located in coding exon 1 of the CHST14 gene, results from a G to C substitution at nucleotide position 138. The methionine at codon 46 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear. |