Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000814422 | SCV000954832 | uncertain significance | Dyskeratosis congenita, autosomal dominant 6 | 2018-12-09 | 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: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The cysteine 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 ACD-related conditions. This variant is present in population databases (rs775602659, ExAC 0.01%). This sequence change replaces tyrosine with cysteine at codon 203 of the ACD protein (p.Tyr203Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. |
Ambry Genetics | RCV002352429 | SCV002657767 | uncertain significance | Inborn genetic diseases | 2024-04-22 | criteria provided, single submitter | clinical testing | The p.Y203C variant (also known as c.608A>G), located in coding exon 4 of the ACD gene, results from an A to G substitution at nucleotide position 608. The tyrosine at codon 203 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. 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. |