ClinVar Miner

Submissions for variant NM_003002.4(SDHD):c.157C>G (p.Pro53Ala)

dbSNP: rs1865656629
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV002242124 SCV001514551 uncertain significance Carney-Stratakis syndrome; Pheochromocytoma; Paragangliomas with sensorineural hearing loss; Cowden syndrome 3 2020-02-24 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals with SDHD-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with alanine at codon 53 of the SDHD protein (p.Pro53Ala). The proline residue is highly conserved and there is a small physicochemical difference between proline and alanine. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The alanine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 RCV002402905 SCV002710092 uncertain significance Hereditary cancer-predisposing syndrome 2022-08-23 criteria provided, single submitter clinical testing The p.P53A variant (also known as c.157C>G), located in coding exon 2 of the SDHD gene, results from a C to G substitution at nucleotide position 157. The proline at codon 53 is replaced by alanine, an amino acid with highly similar properties. This amino acid position is conserved. 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.