ClinVar Miner

Submissions for variant NM_003002.4(SDHD):c.325C>T (p.Gln109Ter) (rs1060503770)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000456537 SCV000554047 pathogenic Carney-Stratakis syndrome; Pheochromocytoma; Paragangliomas 1; Cowden syndrome 3 2019-10-24 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the SDHD gene (p.Gln109*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 51 amino acids of the SDHD protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals and families affected with pheochromocytomas (PCC) or paragangliomas (PGL) (PMID: 11897817, 19454582, 25720320, 30050099). ClinVar contains an entry for this variant (Variation ID: 412498). This variant disrupts the C-terminus of the SDHD protein. Other variant(s) that disrupt this region (p.Leu139Pro) have been determined to be pathogenic (PMID: 21348866, 11391798). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000492697 SCV000581233 pathogenic Hereditary cancer-predisposing syndrome 2018-05-11 criteria provided, single submitter clinical testing The p.Q109* pathogenic mutation (also known as c.325C>T), located in coding exon 4 of the SDHD gene, results from a C to T substitution at nucleotide position 325. This changes the amino acid from a glutamine to a stop codon within coding exon 4. Multiple studies have identified this alteration in patients with pheochromocytomas and/or paragangliomas (Bacca et al. Head Neck. 2011;35(1):23-7; Piccini et al. Endocr Relat Cancer. 2012;19(2):149-55; Petramala et al. Endoc Pract. 2008; 14(3):340-6; Simi et al. J Med Genet. 2005;42(8):e52; Baysal et al. J Med Genet. 2002; 39(3): 178-83. 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.

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