Submissions for variant NM_003001.5(SDHC):c.85C>G (p.Pro29Ala)

gnomAD frequency: 0.00001  dbSNP: rs878854588

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000233108	SCV000287808	uncertain significance	Gastrointestinal stromal tumor; Paragangliomas 3	2023-10-08	criteria provided, single submitter	clinical testing	This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 29 of the SDHC protein (p.Pro29Ala). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SDHC-related conditions. ClinVar contains an entry for this variant (Variation ID: 239458). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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	RCV001018077	SCV001179260	uncertain significance	Hereditary cancer-predisposing syndrome	2023-10-31	criteria provided, single submitter	clinical testing	The p.P29A variant (also known as c.85C>G), located in coding exon 3 of the SDHC gene, results from a C to G substitution at nucleotide position 85. The proline at codon 29 is replaced by alanine, an amino acid with highly similar properties. This amino acid position is highly 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.
GeneDx	RCV003153529	SCV003842506	uncertain significance	not provided	2022-09-16	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV003493542	SCV004243371	uncertain significance	not specified	2024-02-06	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV003998864	SCV004814520	uncertain significance	Hereditary pheochromocytoma-paraganglioma	2023-02-10	criteria provided, single submitter	clinical testing