ClinVar Miner

Submissions for variant NM_004168.4(SDHA):c.615T>A (p.Tyr205Ter)

dbSNP: rs876658486
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000221025 SCV000273780 pathogenic Hereditary cancer-predisposing syndrome 2023-08-30 criteria provided, single submitter clinical testing The p.Y205* pathogenic mutation (also known as c.615T>A), located in coding exon 5 of the SDHA gene, results from a T to A substitution at nucleotide position 615. This changes the amino acid from a tyrosine to a stop codon within coding exon 5. 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000798190 SCV000937792 pathogenic Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 2020-11-27 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in SDHA are known to be pathogenic (PMID: 22974104, 24781757). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with SDHA-related conditions. ClinVar contains an entry for this variant (Variation ID: 230290). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Tyr205*) in the SDHA gene. It is expected to result in an absent or disrupted protein product.
Myriad Genetics, Inc. RCV003316203 SCV004019080 pathogenic Paragangliomas 5 2023-03-29 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.

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