Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002012700 | SCV002279554 | uncertain significance | Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma | 2021-09-18 | criteria provided, single submitter | clinical testing | 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) performed at Invitae indicates that this missense variant is not expected to disrupt SDHB 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. This variant has not been reported in the literature in individuals affected with SDHB-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with histidine at codon 7 of the SDHB protein (p.Leu7His). The leucine residue is weakly conserved and there is a moderate physicochemical difference between leucine and histidine. |
Ambry Genetics | RCV002423212 | SCV002724538 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-05-27 | criteria provided, single submitter | clinical testing | The p.L7H variant (also known as c.20T>A), located in coding exon 1 of the SDHB gene, results from a T to A substitution at nucleotide position 20. The leucine at codon 7 is replaced by histidine, an amino acid with similar properties. This amino acid position is poorly 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. |