ClinVar Miner

Submissions for variant NM_017849.3(TMEM127):c.121A>G (p.Ile41Val) (rs760633411)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000574095 SCV000664467 uncertain significance Hereditary cancer-predisposing syndrome 2019-02-06 criteria provided, single submitter clinical testing The p.I41V variant (also known as c.121A>G), located in coding exon 1 of the TMEM127 gene, results from an A to G substitution at nucleotide position 121. The isoleucine at codon 41 is replaced by valine, an amino acid with highly similar properties. In a study of TMEM127-related pheochromocytomas, this variant was observed in a healthy control population of 170 Caucasians and considered to be a rare polymorphism by the authors (Burnichon N et al. Eur. J. Endocrinol. 2011 Jan; 164(1):141-5). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV000639355 SCV000760927 uncertain significance Hereditary Paraganglioma-Pheochromocytoma Syndromes 2019-12-18 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 41 of the TMEM127 protein (p.Ile41Val). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs760633411, ExAC 0.06%). This variant has not been reported in the literature in individuals with TMEM127-related disease. ClinVar contains an entry for this variant (Variation ID: 480774). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
St. Jude Clinical Genomics Lab, St. Jude Children's Research Hospital RCV000760995 SCV000890910 uncertain significance Acute myeloid leukemia 2016-12-22 criteria provided, single submitter clinical testing

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