ClinVar Miner

Submissions for variant NM_003002.4(SDHD):c.352del (p.Asp118fs) (rs1131691064)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000492559 SCV000581227 pathogenic Hereditary cancer-predisposing syndrome 2018-09-07 criteria provided, single submitter clinical testing The c.352delG pathogenic mutation, located in coding exon 4 of the SDHD gene, results from a deletion of one nucleotide at nucleotide position 352, causing a translational frameshift with a predicted alternate stop codon (p.D118Mfs*17). This alteration was identified in a patient with a SDH-deficient gastrointestinal stromal tumor (GIST) (Miettinen M et al. Am. J. Surg. Pathol., 2013 Feb;37:234-40). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation. As such, this alteration is interpreted as a disease-causing mutation.
Invitae RCV001386868 SCV001587257 pathogenic Carney-Stratakis syndrome; Pheochromocytoma; Paragangliomas 1; Cowden syndrome 3 2020-10-04 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the SDHD gene (p.Asp118Metfs*17). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 42 amino acid(s) of the SDHD protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with gastrointestinal stromal tumor syndrome and paraganglioma (PMID: 23282968, Invitae). ClinVar contains an entry for this variant (Variation ID: 428938). This variant disrupts the p.Gly138 amino acid residue in SDHD. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 29875428, 31492822, Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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