ClinVar Miner

Submissions for variant NM_003002.4(SDHD):c.14G>A (p.Trp5Ter)

dbSNP: rs104894310
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001851719 SCV002238343 pathogenic Carney-Stratakis syndrome; Pheochromocytoma; Paragangliomas with sensorineural hearing loss; Cowden syndrome 3 2021-10-02 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 6916). This premature translational stop signal has been observed in individual(s) with clinical features of paraganglioma-pheochromocytoma syndrome (PMID: 12000816, 25819804, 30050099). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Trp5*) in the SDHD gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SDHD are known to be pathogenic (PMID: 19454582, 19802898).
Ambry Genetics RCV004018584 SCV005019724 pathogenic Hereditary cancer-predisposing syndrome 2024-03-13 criteria provided, single submitter clinical testing The p.W5* pathogenic mutation (also known as c.14G>A), located in coding exon 1 of the SDHD gene, results from a G to A substitution at nucleotide position 14. This changes the amino acid from a tryptophan to a stop codon within coding exon 1. This mutation has been observed in multiple individuals with a personal and/or family history that is consistent with SDHD-related paraganglioma-pheochromocytoma syndrome (Neumann HP et al. N Engl J Med, 2002 May;346:1459-66; Richter S et al. Genet Med, 2019 Mar;21:705-717; White G et al. Endocr Connect, 2022 Feb;11; Ambry internal data). In addition to the clinical data presented in the 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.
OMIM RCV004018583 SCV000027523 pathogenic Paragangliomas 1 2002-05-09 no assertion criteria provided literature only

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