ClinVar Miner

Submissions for variant NM_004168.4(SDHA):c.996_997inv (p.Val333Ile)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000473544 SCV000553886 uncertain significance Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 2023-10-24 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 333 of the SDHA protein (p.Val333Ile). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. 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: 412369). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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 RCV002383837 SCV002694024 uncertain significance Hereditary cancer-predisposing syndrome 2022-09-30 criteria provided, single submitter clinical testing The c.996_997delTGinsCA variant, located in coding exon 8 of the SDHA gene, results from an in-frame deletion of TG and insertion of CA at nucleotide positions 996 to 997. This results in the substitution of the valine residue for an isoleucine residue at codon 333, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be neutral by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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