Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001013540 | SCV001174141 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-07-28 | criteria provided, single submitter | clinical testing | The p.Y629C variant (also known as c.1886A>G), located in coding exon 14 of the SDHA gene, results from an A to G substitution at nucleotide position 1886. The tyrosine at codon 629 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly 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. |
| Labcorp Genetics |
RCV001052870 | SCV001217102 | uncertain significance | Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 | 2021-02-01 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine with cysteine at codon 629 of the SDHA protein (p.Tyr629Cys). The tyrosine residue is moderately conserved and there is a large physicochemical difference between tyrosine and cysteine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with SDHA-related conditions. ClinVar contains an entry for this variant (Variation ID: 820258). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15"). 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. |
| Gene |
RCV003159171 | SCV003852894 | uncertain significance | not provided | 2023-03-28 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Baylor Genetics | RCV003473570 | SCV004200638 | uncertain significance | Dilated cardiomyopathy 1GG | 2023-06-01 | criteria provided, single submitter | clinical testing | |
| Mayo Clinic Laboratories, |
RCV003159171 | SCV005410662 | uncertain significance | not provided | 2024-07-29 | criteria provided, single submitter | clinical testing |