Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000549735 | SCV000651477 | uncertain significance | Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 | 2022-09-06 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 332 of the SDHA protein (p.Pro332Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with paraganglioma (PMID: 31666924). ClinVar contains an entry for this variant (Variation ID: 472424). 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. 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 | RCV000564552 | SCV000674998 | uncertain significance | Hereditary cancer-predisposing syndrome | 2016-03-17 | criteria provided, single submitter | clinical testing | The p.P332S variant (also known as c.994C>T), located in coding exon 8 of the SDHA gene, results from a C to T substitution at nucleotide position 994. The proline at codon 332 is replaced by serine, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.01% (greater than 10000 alleles tested) in our clinical cohort. 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. |
| Fulgent Genetics, |
RCV000765831 | SCV000897226 | uncertain significance | Leigh syndrome; Mitochondrial complex II deficiency, nuclear type 1; Dilated cardiomyopathy 1GG; Paragangliomas 5 | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| Ce |
RCV002263789 | SCV002544922 | uncertain significance | not provided | 2022-06-01 | criteria provided, single submitter | clinical testing | SDHA: PM2 |