Description
This variant is denoted SDHD c.275A>T at the cDNA level, p.Asp92Val (D92V) at the protein level, and results in the change of an Aspartic Acid to a Valine (GAC>GTC). This variant has not, to our knowledge, been published in the literature as pathogenic or benign; however, another variant at the same residue, SDHD Asp92Tyr, is a well described Dutch pathogenic founder variant (van Schothorst 1998, Hensen 2010). SDHD Asp92Val was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Aspartic Acid and Valine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. SDHD Asp92Val occurs at a position that is conserved across species and is located in the transmembrane helical domain (UniProt). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on the currently available evidence, we consider SDHD Asp92Val to be a likely pathogenic variant.
# | Sample | Method | Observation |
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Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
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1 | germline | yes | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |