NM_017849.4(TMEM127):c.570del (p.Thr191fs) AND Hereditary Paraganglioma-Pheochromocytoma Syndromes

Clinical significance:Likely pathogenic (Last evaluated: Feb 27, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001056017.2

Allele description [Variation Report for NM_017849.4(TMEM127):c.570del (p.Thr191fs)]

NM_017849.4(TMEM127):c.570del (p.Thr191fs)

Gene:
TMEM127:transmembrane protein 127 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
2q11.2
Genomic location:
Preferred name:
NM_017849.4(TMEM127):c.570del (p.Thr191fs)
HGVS:
  • NC_000002.12:g.96253956del
  • NG_027695.1:g.17059del
  • NM_001193304.3:c.570del
  • NM_017849.3:c.570del
  • NM_017849.4:c.570delMANE SELECT
  • NP_001180233.1:p.Thr191fs
  • NP_060319.1:p.Thr191fs
  • NP_060319.1:p.Thr191fs
  • LRG_528t1:c.570del
  • LRG_528:g.17059del
  • LRG_528p1:p.Thr191fs
  • NC_000002.11:g.96919693del
  • NC_000002.11:g.96919694del
  • NM_017849.3:c.570delC
Protein change:
T191fs
Links:
dbSNP: rs1215337884
NCBI 1000 Genomes Browser:
rs1215337884
Molecular consequence:
  • NM_001193304.3:c.570del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_017849.3:c.570del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_017849.4:c.570del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Hereditary Paraganglioma-Pheochromocytoma Syndromes (PGL-PCC)
Synonyms:
Hereditary Paragangliomas and Pheochromocytomas
Identifiers:
MONDO: MONDO:0017366; MedGen: C1708353

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001220436Invitaecriteria provided, single submitter
Likely pathogenic
(Feb 27, 2019)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Novel SDHB and TMEM127 Mutations in Patients with Pheochromocytoma/Paraganglioma Syndrome.

Patócs A, Lendvai NK, Butz H, Liko I, Sapi Z, Szucs N, Toth G, Grolmusz VK, Igaz P, Toth M, Rácz K.

Pathol Oncol Res. 2016 Oct;22(4):673-9. doi: 10.1007/s12253-016-0050-0. Epub 2016 Mar 9.

PubMed [citation]
PMID:
26960314

Pheochromocytomatosis associated with a novel TMEM127 mutation.

Yu R, Sharaga D, Donner C, Palma Diaz MF, Livhits MJ, Yeh MW.

Endocrinol Diabetes Metab Case Rep. 2017;2017. doi:pii: 17-0026. 10.1530/EDM-17-0026.

PubMed [citation]
PMID:
28567294
PMCID:
PMC5445434
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001220436.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change results in a frameshift in the TMEM127 gene (p.Thr191Argfs*116). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 48 amino acids of the TMEM127 protein and extend the protein by an additional 67 amino acids. This variant is not present in population databases (ExAC no frequency). The p.Thr191Argfs*116 variant has been observed in individuals with pheochromocytoma (PMID: 26960314,28567294, Invitae). ClinVar contains an entry for this variant (Variation ID: 486549). This variant disrupts the C-terminus of the TMEM127 protein. Other variant(s) that disrupt this region (p.Met214Serfs98*) have been observed in individuals with TMEM127-related conditions (PMID: 21156949). 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 25, 2021

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