NM_017849.3(TMEM127):c.308del (p.Gly103fs) AND Hereditary Paraganglioma-Pheochromocytoma Syndromes

Clinical significance:Likely pathogenic (Last evaluated: Apr 7, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000152047.2

Allele description [Variation Report for NM_017849.3(TMEM127):c.308del (p.Gly103fs)]

NM_017849.3(TMEM127):c.308del (p.Gly103fs)

Gene:
TMEM127:transmembrane protein 127 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
2q11.2
Genomic location:
Preferred name:
NM_017849.3(TMEM127):c.308del (p.Gly103fs)
HGVS:
  • NC_000002.12:g.96254936del
  • NG_027695.1:g.16080del
  • NM_001193304.3:c.308del
  • NM_017849.3:c.308del
  • NP_001180233.1:p.Gly103fs
  • NP_060319.1:p.Gly103fs
  • LRG_528t1:c.308del
  • LRG_528:g.16080del
  • LRG_528p1:p.Gly103fs
  • NC_000002.11:g.96920672delC
  • NC_000002.11:g.96920674del
  • NM_017849.2:c.308delG
  • p.Gly103AlafsX21
Protein change:
G103fs
Links:
dbSNP: rs727503490
NCBI 1000 Genomes Browser:
rs727503490
Molecular consequence:
  • NM_001193304.3:c.308del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_017849.3:c.308del - frameshift variant - [Sequence Ontology: SO:0001589]
Observations:
1

Condition(s)

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

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000200639Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicinecriteria provided, single submitter
Likely pathogenic
(Apr 7, 2016)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided61not providednot providednot providedclinical testing

Citations

PubMed

Familial pheochromocytoma and renal cell carcinoma syndrome: TMEM127 as a novel candidate gene for the association.

Hernandez KG, Ezzat S, Morel CF, Swallow C, Otremba M, Dickson BC, Asa SL, Mete O.

Virchows Arch. 2015 Jun;466(6):727-32. doi: 10.1007/s00428-015-1755-2. Epub 2015 Mar 24.

PubMed [citation]
PMID:
25800244

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]
PMID:
24033266
PMCID:
PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, SCV000200639.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided6not providednot providedclinical testing PubMed (2)

Description

The p.Gly103fs variant in TMEM127 has been identified in 1 individual with pheoc hromocytomas and renal cell carcinoma (Hernandez 2015, LMM data). It has not be en identified in large population studies. This variant is predicted to cause a frameshift, which alters the protein?s amino acid sequence beginning at position 103 and leads to a premature termination codon 21 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Multiple heterozygous variants in TMEM127 leading to a frameshift and predicted truncate d or absent protein have been reported in individuals with pheochromocytomas. In summary, although additional studies are required to fully establish its clinic al significance, the p.Gly103fs variant is likely pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided6not provided1not provided

Last Updated: Jul 7, 2021

Support Center