ClinVar Miner

Submissions for variant NM_003002.4(SDHD):c.13_14del (p.Trp5fs) (rs1566690018)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000756633 SCV000884505 pathogenic not provided 2018-05-17 criteria provided, single submitter clinical testing The SDHD c.13_14delTG; p.Trp5fs variant, to our knowledge, is not reported in the medical literature or in gene-specific databases. However, at least one start loss variant and one nonsense variant in codon 5 have been described in the literature in individuals with paraganglioma or pheochromocytoma (Andrews 2017). The SDHD c.13_14delTG variant is also absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. This variant causes a frameshift by deleting two nucleotides, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Additionally, loss of function frameshift and nonsense variants are a known mechanism of disease (Turchini 2018). Considering available information, this variant is classified as pathogenic. References: Andrews KA et al. Tumour risks and genotype-phenotype correlations associated with germline variants in succinate dehydrogenase subunit genes SDHB, SDHC and SDHD. J Med Genet. 2018 Jan 31. Turchini J et al. Pathology and genetics of phaeochromocytoma and paraganglioma. Histopathology. 2018 Jan;72(1):97-105.
Invitae RCV000811490 SCV000951758 pathogenic Carney-Stratakis syndrome; Pheochromocytoma; Paragangliomas 1; Cowden syndrome 3 2018-12-19 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp5Glufs*63) in the SDHD gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SDHD-related conditions. Loss-of-function variants in SDHD are known to be pathogenic (PMID: 19454582, 19802898). For these reasons, this variant has been classified as Pathogenic.

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