ClinVar Miner

Submissions for variant NM_004168.4(SDHA):c.554dup (p.Ala186fs)

dbSNP: rs1173940446
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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 RCV001384161 SCV001583546 pathogenic Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 2022-08-12 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1071644). This variant has not been reported in the literature in individuals affected with SDHA-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ala186Glyfs*9) 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).
Ambry Genetics RCV002350731 SCV002649952 pathogenic Hereditary cancer-predisposing syndrome 2022-09-28 criteria provided, single submitter clinical testing The c.554dupA variant, located in coding exon 5 of the SDHA gene, results from a duplication of A at nucleotide position 554, causing a translational frameshift with a predicted alternate stop codon (p.A186Gfs*9). This alteration was identified in an individual with a personal history of a head/neck paraganglioma diagnosed under age 30 (Gieldon L et al. Cancers (Basel), 2019 Jun;11:). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Of note, this alteration is also designated as "c.553_554insA (p.Ala186fs)" in published literature. 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.
Revvity Omics, Revvity RCV003132489 SCV003812695 likely pathogenic not provided 2022-03-14 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV004037665 SCV004930750 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.

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