ClinVar Miner

Submissions for variant NM_017849.3(TMEM127):c.182G>C (p.Cys61Ser) (rs886056448)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000362855 SCV000432548 uncertain significance Pheochromocytoma 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Ambry Genetics RCV001013341 SCV001173920 uncertain significance Hereditary cancer-predisposing syndrome 2019-09-12 criteria provided, single submitter clinical testing The p.C61S variant (also known as c.182G>C), located in coding exon 1 of the TMEM127 gene, results from a G to C substitution at nucleotide position 182. The cysteine at codon 61 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV001064699 SCV001229613 uncertain significance Hereditary Paraganglioma-Pheochromocytoma Syndromes 2020-08-02 criteria provided, single submitter clinical testing This sequence change replaces cysteine with serine at codon 61 of the TMEM127 protein (p.Cys61Ser). The cysteine residue is highly conserved and there is a moderate physicochemical difference between cysteine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TMEM127-related conditions. ClinVar contains an entry for this variant (Variation ID: 337507). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably 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.

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