ClinVar Miner

Submissions for variant NM_004168.4(SDHA):c.46_52dup (p.Leu18fs)

dbSNP: rs1560980939
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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 RCV000696009 SCV000824550 pathogenic Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 2024-01-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu18Profs*23) in the SDHA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SDHA are known to be pathogenic (PMID: 22974104, 24781757). This variant is not present in population databases (gnomAD no frequency). 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: 574154). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV003128647 SCV003805382 likely pathogenic not provided 2023-02-16 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD)
Myriad Genetics, Inc. RCV004026357 SCV004933820 pathogenic Paragangliomas 5 2024-02-07 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Ambry Genetics RCV004948603 SCV005496518 pathogenic Hereditary cancer-predisposing syndrome 2024-09-19 criteria provided, single submitter clinical testing The c.46_52dupCTGGCGC pathogenic mutation, located in coding exon 1 of the SDHA gene, results from a duplication of CTGGCGC at nucleotide position 46, causing a translational frameshift with a predicted alternate stop codon (p.L18Pfs*23). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

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