ClinVar Miner

Submissions for variant NM_003001.5(SDHC):c.460del (p.Val154fs)

dbSNP: rs786201665
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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 RCV000164065 SCV000214675 uncertain significance Hereditary cancer-predisposing syndrome 2018-11-02 criteria provided, single submitter clinical testing The c.460delG variant, located in coding exon 6 of the SDHC gene, results from a deletion of one nucleotide at position 460, causing a translational frameshift with a predicted alternate stop codon (p.V154Lfs*117). Frameshifts are typically deleterious in nature, however, this frameshift occurs at the 3' terminus of SDHC, is not expected to trigger nonsense-mediated mRNA decay, and results in the elongation of the protein by 100 amino acids. The exact functional impact of these inserted amino acids is unknown at this time. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001850290 SCV002294873 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 3 2021-04-22 criteria provided, single submitter clinical testing This variant has been observed in individual(s) with paraganglioma (Invitae). ClinVar contains an entry for this variant (Variation ID: 184753). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts a region of the protein in which other variant(s) (p.Leu158Pro) have been observed in individuals with SDHC-related conditions (PMID: 12807974, 30877234). This suggests that this may be a clinically significant region of the SDHC protein. This variant is not present in population databases (ExAC no frequency). This sequence change results in a frameshift in the SDHC gene (p.Val154Leufs*117). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 16 amino acid(s) of the SDHC protein and extend the protein by 100 additional amino acid residues.

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