ClinVar Miner

Submissions for variant NM_003001.5(SDHC):c.386G>A (p.Trp129Ter)

dbSNP: rs1672294906
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Department of Medical Genetics, College of Basic Medicine, Army Medical University RCV001256199 SCV001422317 pathogenic Paragangliomas 3 2020-07-15 criteria provided, single submitter clinical testing The Trp129Ter variant in SDHC creates a premature nonsense codon, which has been reported in ClinVar as Pathogenic in Hereditary cancer-predisposing syndrome. This variant was found in a Chinese patient with Paragangliomas and the data is high quality.
Labcorp Genetics (formerly Invitae), Labcorp RCV001879958 SCV002233571 pathogenic Gastrointestinal stromal tumor; Paragangliomas 3 2022-07-26 criteria provided, single submitter clinical testing Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the SDHC protein in which other variant(s) (p.Arg133*) have been determined to be pathogenic (PMID: 23083876, 24423348, 24758179, 27700540). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 978229). This premature translational stop signal has been observed in individual(s) with rhabdomyosarcoma (PMID: 33372952). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp129*) in the SDHC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 41 amino acid(s) of the SDHC protein.
Myriad Genetics, Inc. RCV001256199 SCV004933609 pathogenic Paragangliomas 3 2023-12-18 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.
Ambry Genetics RCV004671305 SCV005161236 likely pathogenic Hereditary cancer-predisposing syndrome 2024-04-24 criteria provided, single submitter clinical testing The p.W129* variant (also known as c.386G>A), located in coding exon 5 of the SDHC gene, results from a G to A substitution at nucleotide position 386. This changes the amino acid from a tryptophan to a stop codon within coding exon 5. This alteration occurs at the 3' terminus of theSDHC gene, is not expected to trigger nonsense-mediated mRNA decay, and only impacts the last 41 amino acids of the protein. However, premature stop codons are typically deleterious in nature and the impacted region is critical for protein function (Ambry internal data). This variant was detected in a pediatric patient with embryonal rhabdomyosarcoma (Li H et al. J Natl Cancer Inst, 2021 Jul;113:875-883). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine RCV001257556 SCV001434382 likely pathogenic Rhabdomyosarcoma 2020-09-01 no assertion criteria provided provider interpretation

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