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NM_000243.3(MEFV):c.436C>T (p.Gln146Ter) AND not specified

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Oct 18, 2018
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000781527.1

Allele description [Variation Report for NM_000243.3(MEFV):c.436C>T (p.Gln146Ter)]

NM_000243.3(MEFV):c.436C>T (p.Gln146Ter)

Gene:
MEFV:MEFV innate immunity regulator, pyrin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
16p13.3
Genomic location:
Preferred name:
NM_000243.3(MEFV):c.436C>T (p.Gln146Ter)
HGVS:
  • NC_000016.10:g.3254632G>A
  • NG_007871.1:g.6996C>T
  • NM_000243.3:c.436C>TMANE SELECT
  • NM_001198536.2:c.277+1679C>T
  • NP_000234.1:p.Gln146Ter
  • NP_000234.1:p.Gln146Ter
  • LRG_190t1:c.436C>T
  • LRG_190:g.6996C>T
  • LRG_190p1:p.Gln146Ter
  • NC_000016.9:g.3304632G>A
  • NM_000243.2:c.436C>T
Protein change:
Q146*
Links:
dbSNP: rs876660990
NCBI 1000 Genomes Browser:
rs876660990
Molecular consequence:
  • NM_001198536.2:c.277+1679C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000243.3:c.436C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000919628Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Uncertain significance
(Oct 18, 2018) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

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Summary from all submissions

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

Citations

PubMed

Monogenic Autoinflammatory Diseases with Mendelian Inheritance: Genes, Mutations, and Genotype/Phenotype Correlations.

Martorana D, Bonatti F, Mozzoni P, Vaglio A, Percesepe A.

Front Immunol. 2017;8:344. doi: 10.3389/fimmu.2017.00344. Review.

PubMed [citation]
PMID:
28421071
PMCID:
PMC5376573

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000919628.1

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

Description

Variant summary: MEFV c.436C>T (p.Gln146X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 233434 control chromosomes (ExAC). To our knowledge, no occurrence of c.436C>T in individuals affected with Familial Mediterranean Fever and no experimental evidence demonstrating its impact on protein function have been reported. However, HGMD cites two nonsense variants, p.Tyr471X and p.Tyr688X, downstream of this variant in affected individuals (Notarnicola_2011, Berdeli_2011). In addition, a ClinVar submssion from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as uncertain significance. Based on the evidence outlined above, and considering that nonsense variants in this gene are very rare, the variant was classified as VUS-possibly pathogenic.

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

Last Updated: Sep 29, 2024