Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003783019 | SCV004603306 | uncertain significance | Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 | 2024-01-06 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 102 of the SDHA protein (p.Ala102Pro). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SDHA-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SDHA protein function. 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 | RCV004374384 | SCV005021382 | uncertain significance | Hereditary cancer-predisposing syndrome | 2014-10-13 | criteria provided, single submitter | clinical testing | The p.A102P variant (also known as c.304G>C), located in coding exon 3 of the SDHA gene, results from a G to C substitution at nucleotide position 304. The alanine at codon 102 is replaced by proline, an amino acid with highly 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 6500 samples (13000 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.10% (greater than 1000 alleles tested) in our clinical cohort, including this individual. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be probably damaging and deleterious by PolyPhen and SIFT in silico analyses, respectively. Since supporting evidence is limited at this time, the clinical significance of p.A102P remains unclear. |