NM_000492.4(CFTR):c.1712T>C (p.Leu571Ser) AND Cystic fibrosis

Clinical significance:Likely pathogenic (Last evaluated: Jan 21, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000577164.2

Allele description [Variation Report for NM_000492.4(CFTR):c.1712T>C (p.Leu571Ser)]

NM_000492.4(CFTR):c.1712T>C (p.Leu571Ser)

Gene:
CFTR:CF transmembrane conductance regulator [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7q31.2
Genomic location:
Preferred name:
NM_000492.4(CFTR):c.1712T>C (p.Leu571Ser)
HGVS:
  • NC_000007.14:g.117590385T>C
  • NG_016465.4:g.129602T>C
  • NM_000492.3:c.1712T>C
  • NM_000492.4:c.1712T>CMANE SELECT
  • NP_000483.3:p.Leu571Ser
  • NP_000483.3:p.Leu571Ser
  • LRG_663t1:c.1712T>C
  • LRG_663:g.129602T>C
  • LRG_663p1:p.Leu571Ser
  • NC_000007.13:g.117230439T>C
  • P13569:p.Leu571Ser
Protein change:
L571S
Links:
UniProtKB: P13569#VAR_000193; dbSNP: rs397508280
NCBI 1000 Genomes Browser:
rs397508280
Molecular consequence:
  • NM_000492.3:c.1712T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000492.4:c.1712T>C - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000679122ClinVar Staff, National Center for Biotechnology Information (NCBI)no assertion providednot providedgermlineliterature only

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

SCV001360491Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Likely pathogenic
(Jan 21, 2019)
germlineclinical testing

PubMed (10)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedliterature only
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Genetic evidence for CFTR dysfunction in Japanese: background for chronic pancreatitis.

Fujiki K, Ishiguro H, Ko SB, Mizuno N, Suzuki Y, Takemura T, Yamamoto A, Yoshikawa T, Kitagawa M, Hayakawa T, Sakai Y, Takayama T, Saito M, Kondo T, Naruse S.

J Med Genet. 2004 May;41(5):e55. No abstract available.

PubMed [citation]
PMID:
15121783
PMCID:
PMC1735764

Spectrum of mutations in the CFTR gene in cystic fibrosis patients of Spanish ancestry.

Alonso MJ, Heine-Suñer D, Calvo M, Rosell J, Giménez J, Ramos MD, Telleria JJ, Palacio A, Estivill X, Casals T.

Ann Hum Genet. 2007 Mar;71(Pt 2):194-201.

PubMed [citation]
PMID:
17331079
See all PubMed Citations (10)

Details of each submission

From ClinVar Staff, National Center for Biotechnology Information (NCBI), SCV000679122.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001360491.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (10)

Description

Variant summary: CFTR c.1712T>C (p.Leu571Ser) results in a non-conservative amino acid change located in the AAA+ ATPase domain (IPR003593) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 245736 control chromosomes (gnomAD and publication). c.1712T>C has been reported in the literature in a homozygous and at least two compound heterozygote individuals affected with Cystic Fibrosis (Onay 1998, Varon 1995, Lucarelli 2015, Lucarelli 2017). These data indicate that the variant may be associated with disease. In addition, variants located nearby this variant, Y569H, Y569D, Y569C, D572N and P574H, have been reported in HGMD associated with cystic fibrosis, thus suggesting this region is important for CFTR protein function. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was 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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