Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000037720 | SCV000061382 | uncertain significance | not specified | 2013-01-29 | criteria provided, single submitter | clinical testing | The Leu139Phe variant in SDHB has not been previously identified in the literatu re or by our laboratory. This variant has not been identified in large and broad European American and African American populations by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS/), though it may be common in other populations. Computational analyses (biochemical amino acid properties, conserva tion, AlignGVGD, PolyPhen2, and SIFT) suggest that the Leu139Phe variant may imp act the protein, though this information is not predictive enough to determine p athogenicity. In summary, additional information is needed to fully assess the c linical significance of the Leu139Phe variant. |
| Ambry Genetics | RCV000565686 | SCV000675090 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2017-08-29 | criteria provided, single submitter | clinical testing | The p.L139F variant (also known as c.415C>T), located in coding exon 4 of the SDHB gene, results from a C to T substitution at nucleotide position 415. The leucine at codon 139 is replaced by phenylalanine, an amino acid with highly similar properties. This alteration was detected in a 12 year old with a paraganglioma, which demonstrated absence of the SDHB protein by immunohistochemistry (Liu et al. Hong Kong Journal of Paediatrics. 2015; 20(3):196). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |