Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000521235 | SCV000621879 | uncertain significance | not provided | 2021-06-17 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 27535533) |
| Invitae | RCV001858045 | SCV002217336 | uncertain significance | Ehlers-Danlos syndrome, musculocontractural type | 2021-05-13 | 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 histidine 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. ClinVar contains an entry for this variant (Variation ID: 453025). This variant is present in population databases (rs775350610, ExAC 0.002%). This sequence change replaces tyrosine with histidine at codon 147 of the CHST14 protein (p.Tyr147His). The tyrosine residue is highly conserved and there is a moderate physicochemical difference between tyrosine and histidine. |
| Ambry Genetics | RCV002329245 | SCV002633318 | uncertain significance | Cardiovascular phenotype | 2023-01-12 | criteria provided, single submitter | clinical testing | The p.Y147H variant (also known as c.439T>C), located in coding exon 1 of the CHST14 gene, results from a T to C substitution at nucleotide position 439. The tyrosine at codon 147 is replaced by histidine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species, and histidine is the reference amino acid in other 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. |