NM_000492.3(CFTR):c.1518C>G (p.Ile506Met) AND Cystic fibrosis

Clinical significance:Uncertain significance (Last evaluated: Jul 15, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000046332.4

Allele description [Variation Report for NM_000492.3(CFTR):c.1518C>G (p.Ile506Met)]

NM_000492.3(CFTR):c.1518C>G (p.Ile506Met)

Genes:
CFTR:CF transmembrane conductance regulator [Gene - OMIM - HGNC]
CFTR-AS1:CFTR antisense RNA 1 [Gene - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7q31.2
Genomic location:
Preferred name:
NM_000492.3(CFTR):c.1518C>G (p.Ile506Met)
HGVS:
  • NC_000007.14:g.117559589C>G
  • NG_016465.4:g.98806C>G
  • NM_000492.3:c.1518C>G
  • NP_000483.3:p.Ile506Met
  • LRG_663t1:c.1518C>G
  • LRG_663:g.98806C>G
  • LRG_663p1:p.Ile506Met
  • NC_000007.13:g.117199643C>G
  • P13569:p.Ile506Met
Protein change:
I506M
Links:
UniProtKB: P13569#VAR_009901; dbSNP: rs1800092
NCBI 1000 Genomes Browser:
rs1800092
Molecular consequence:
  • NM_000492.3:c.1518C>G - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Cystic fibrosis (CF)
Synonyms:
Mucoviscidosis
Identifiers:
MONDO: MONDO:0009061; MedGen: C0010674; Orphanet: 586; OMIM: 219700

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000256831Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Geneticsno assertion criteria providedPathogenic
(Oct 19, 2015)
unknownclinical testing

SCV001535098Invitaecriteria provided, single submitter
Uncertain significance
(Jul 15, 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
Indianunknownyes11not providednot providednot providedclinical testing

Citations

PubMed

Mutation analysis in 600 French cystic fibrosis patients.

Chevalier-Porst F, Bonardot AM, Gilly R, Chazalette JP, Mathieu M, Bozon D.

J Med Genet. 1994 Jul;31(7):541-4.

PubMed [citation]
PMID:
7525963
PMCID:
PMC1049976

A haplotype framework for cystic fibrosis mutations in Iran.

Elahi E, Khodadad A, Kupershmidt I, Ghasemi F, Alinasab B, Naghizadeh R, Eason RG, Amini M, Esmaili M, Esmaeili Dooki MR, Sanati MH, Davis RW, Ronaghi M, Thorstenson YR.

J Mol Diagn. 2006 Feb;8(1):119-27.

PubMed [citation]
PMID:
16436643
PMCID:
PMC1867567
See all PubMed Citations (4)

Details of each submission

From Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics, SCV000256831.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1Indian1not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownyesnot providednot providednot provided1not provided1not provided

From Invitae, SCV001535098.1

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

Description

This sequence change replaces isoleucine with methionine at codon 506 of the CFTR protein (p.Ile506Met). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with cystic fibrosis (PMID: 7525963, Invitae). ClinVar contains an entry for this variant (Variation ID: 53278). 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). This variant disrupts the p.Ile506 amino acid residue in CFTR. Other variant(s) that disrupt this residue have been observed in individuals with cystic fibrosis (PMID: 16436643, 7509683), which suggests that this may be a clinically significant amino acid residue. 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.

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

Last Updated: Apr 12, 2021

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