Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000705255 | SCV000834244 | uncertain significance | Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 | 2021-01-31 | criteria provided, single submitter | clinical testing | 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. This variant has not been reported in the literature in individuals with SDHA-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces tryptophan with cysteine at codon 558 of the SDHA protein (p.Trp558Cys). The tryptophan residue is highly conserved and there is a large physicochemical difference between tryptophan and cysteine. |
Ambry Genetics | RCV002397477 | SCV002712773 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-09 | criteria provided, single submitter | clinical testing | The p.W558C variant (also known as c.1674G>T), located in coding exon 13 of the SDHA gene, results from a G to T substitution at nucleotide position 1674. The tryptophan at codon 558 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |