ClinVar Miner

Submissions for variant NM_004168.4(SDHA):c.1652C>T (p.Thr551Met)

gnomAD frequency: 0.00002  dbSNP: rs181238392
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000458208 SCV000553921 uncertain significance Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 2024-01-29 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 551 of the SDHA protein (p.Thr551Met). This variant is present in population databases (rs181238392, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with SDHA-related conditions. ClinVar contains an entry for this variant (Variation ID: 412397). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SDHA protein function with a negative predictive value of 95%. 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 RCV000569746 SCV000674999 uncertain significance Hereditary cancer-predisposing syndrome 2023-04-11 criteria provided, single submitter clinical testing The p.T551M variant (also known as c.1652C>T), located in coding exon 12 of the SDHA gene, results from a C to T substitution at nucleotide position 1652. The threonine at codon 551 is replaced by methionine, an amino acid with 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.
Counsyl RCV000662939 SCV000785896 uncertain significance Paragangliomas 5 2018-01-04 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002475896 SCV002777502 uncertain significance Mitochondrial complex II deficiency, nuclear type 1; Dilated cardiomyopathy 1GG; Paragangliomas 5; Neurodegeneration with ataxia and late-onset optic atrophy 2021-08-31 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV000662939 SCV004018575 uncertain significance Paragangliomas 5 2023-04-20 criteria provided, single submitter clinical testing This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
GenomeConnect - Invitae Patient Insights Network RCV000662939 SCV004228538 not provided Paragangliomas 5 no assertion provided phenotyping only Variant interpreted as Uncertain significance and reported on 03-11-2019 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.

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