NM_000243.3(MEFV):c.1459G>C (p.Val487Leu) AND not specified

Clinical significance:Uncertain significance (Last evaluated: Sep 28, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000439116.3

Allele description [Variation Report for NM_000243.3(MEFV):c.1459G>C (p.Val487Leu)]

NM_000243.3(MEFV):c.1459G>C (p.Val487Leu)

Gene:
MEFV:MEFV innate immuity regulator, pyrin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
16p13.3
Genomic location:
Preferred name:
NM_000243.3(MEFV):c.1459G>C (p.Val487Leu)
HGVS:
  • NC_000016.10:g.3247144C>G
  • NG_007871.1:g.14484G>C
  • NM_000243.3:c.1459G>CMANE SELECT
  • NM_001198536.2:c.826G>C
  • NP_000234.1:p.Val487Leu
  • NP_000234.1:p.Val487Leu
  • NP_001185465.2:p.Val276Leu
  • LRG_190t1:c.1459G>C
  • LRG_190:g.14484G>C
  • LRG_190p1:p.Val487Leu
  • NC_000016.9:g.3297144C>G
  • NM_000243.2:c.1459G>C
Protein change:
V276L
Links:
dbSNP: rs104895100
NCBI 1000 Genomes Browser:
rs104895100
Molecular consequence:
  • NM_000243.3:c.1459G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001198536.2:c.826G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001437218Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Uncertain significance
(Sep 28, 2020)
germlineclinical testing

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

Citation Link

Summary from all submissions

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

Citations

PubMed

Comprehensive analysis of mutations in the MEFV gene reveal that the location and not the substitution type determines symptom severity in FMF.

Moradian MM, Babikyan D, Banoian D, Hayrapetyan H, Manvelyan H, Avanesian N, Sarkisian T.

Mol Genet Genomic Med. 2017 Nov;5(6):742-750. doi: 10.1002/mgg3.336. Epub 2017 Oct 9.

PubMed [citation]
PMID:
29178647
PMCID:
PMC5702578
See all PubMed Citations (4)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001437218.1

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

Description

Variant summary: MEFV c.1459G>C (p.Val487Leu) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00077 in 282892 control chromosomes in the gnomAD database, including 2 homozygotes. This frequency is not significantly higher than expected for a pathogenic variant in MEFV causing Familial Mediterranean Fever (0.00077 vs 0.022), allowing no conclusion about variant significance. c.1459G>C has been reported in the literature in an individual (heterozygous) with clinically suspected Familial Mediterranean Fever (Gumus_2018). In 2018, the experts international study group for systemic autoinflammatory diseases (INSAID) reported classification and status of this variant as Unsolved (Van Gijn_2018). Recently however, Accetturo et al proposed a classification of likely benign (Accetturo _2019) based on a variant metapredictor tool REVEL (Rare Exome Variant Ensemble Learner) for this variant. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as likely benign. Based on the evidence outlined above, the variant was classified as VUS-possibly benign.

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

Last Updated: Dec 4, 2021

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