ClinVar Miner

Submissions for variant NM_017849.4(TMEM127):c.512delinsGCC (p.Val171fs)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001246329 SCV001419674 likely pathogenic Hereditary Paraganglioma-Pheochromocytoma Syndromes 2019-07-13 criteria provided, single submitter clinical testing This sequence change results in a frameshift in the TMEM127 gene (p.Val171Glyfs*137). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 68 amino acids of the TMEM127 protein and extend the protein by an additional 68 amino acids. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with head and neck paraganglioma (PMID: 23666964). This variant disrupts the C-terminus of the TMEM127 protein. Other variant(s) that disrupt this region (c.532dup, c.543_555dup, c.572del) have been observed in individuals with TMEM127-related conditions (PMID: 26960314, 28855235, 28384794). This suggests that this may be a clinically significant region of the protein. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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