ClinVar Miner

Submissions for variant NM_004168.4(SDHA):c.1055G>A (p.Arg352Gln) (rs199844384)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000563279 SCV000674918 uncertain significance Hereditary cancer-predisposing syndrome 2017-10-11 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Counsyl RCV000411606 SCV000489339 uncertain significance Paragangliomas 5 2016-09-20 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000765832 SCV000897227 uncertain significance Leigh syndrome; Mitochondrial complex II deficiency; Dilated cardiomyopathy 1GG; Paragangliomas 5 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000498298 SCV000590005 uncertain significance not provided 2018-11-20 criteria provided, single submitter clinical testing The R352Q variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R352Q variant is observed in 1/8654 (0.01%) alleles from individuals of East Asian background, in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R352Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. In summary, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000463749 SCV000553876 uncertain significance Mitochondrial complex II deficiency; Paragangliomas 5 2018-12-26 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 352 of the SDHA protein (p.Arg352Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs199844384, ExAC 0.01%). This variant has not been reported in the literature in individuals with SDHA-related disease. ClinVar contains an entry for this variant (Variation ID: 371975). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.

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