ClinVar Miner

Submissions for variant NM_004168.4(SDHA):c.453C>A (p.Val151=)

gnomAD frequency: 0.00006  dbSNP: rs138917116
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000475275 SCV000553915 likely benign Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 2024-01-13 criteria provided, single submitter clinical testing
Ambry Genetics RCV001022664 SCV001184424 likely benign Hereditary cancer-predisposing syndrome 2018-03-29 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV003230266 SCV003928125 uncertain significance Paragangliomas 5 2023-04-20 criteria provided, single submitter clinical testing The SDHA c.453C>A (p.Val151=) synonymous change has a maximum subpopulation frequency of 0.005% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). Algorithms that predict the impact of sequence changes on splicing indicate that this change may create or activate a cryptic donor splice site, but RNA studies indicate no splicing effect (internal data). To our knowledge, this variant has not been reported in individuals with SDHA-associated tumors. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.
GeneDx RCV004760520 SCV005371733 uncertain significance not provided 2023-06-30 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge; In silico analysis suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.

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