NM_000492.4(CFTR):c.1052C>G (p.Thr351Ser) AND Cystic fibrosis

Clinical significance:Uncertain significance (Last evaluated: Jul 22, 2021)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000046212.8

Allele description [Variation Report for NM_000492.4(CFTR):c.1052C>G (p.Thr351Ser)]

NM_000492.4(CFTR):c.1052C>G (p.Thr351Ser)

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.1052C>G (p.Thr351Ser)
HGVS:
  • NC_000007.14:g.117540282C>G
  • NG_016465.4:g.79499C>G
  • NM_000492.3:c.1052C>G
  • NM_000492.4:c.1052C>GMANE SELECT
  • NP_000483.3:p.Thr351Ser
  • NP_000483.3:p.Thr351Ser
  • LRG_663t1:c.1052C>G
  • LRG_663:g.79499C>G
  • LRG_663p1:p.Thr351Ser
  • NC_000007.13:g.117180336C>G
  • NM_000492.4:c.1052C>G
  • P13569:p.Thr351Ser
Protein change:
T351S
Links:
UniProtKB: P13569#VAR_009899; dbSNP: rs1800086
NCBI 1000 Genomes Browser:
rs1800086
Molecular consequence:
  • NM_000492.3:c.1052C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000492.4:c.1052C>G - missense variant - [Sequence Ontology: SO:0001583]
Functional consequence:
Normal function

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
SCV000074225Invitaecriteria provided, single submitter
Uncertain significance
(Nov 13, 2019)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

SCV000886356Mendelicscriteria provided, single submitter
Uncertain significance
(Nov 5, 2018)
unknownclinical testing

Citation Link,

SCV001822034Nilou-Genome Labcriteria provided, single submitter
Uncertain significance
(Jul 22, 2021)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

Molecular evaluation of CFTR sequence variants in male infertility of testicular origin.

Larriba S, Bonache S, Sarquella J, Ramos MD, Giménez J, Bassas L, Casals T.

Int J Androl. 2005 Oct;28(5):284-90.

PubMed [citation]
PMID:
16128988

Cystic hygroma in Saudi Arabian children.

al-Samarrai AY, Jawad AJ, al-Rabeeah A, Patel PJ, Yohanan MD.

J R Coll Surg Edinb. 1990 Jun;35(3):178-80.

PubMed [citation]
PMID:
2395135
See all PubMed Citations (7)

Details of each submission

From Invitae, SCV000074225.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

This sequence change replaces threonine with serine at codon 351 of the CFTR protein (p.Thr351Ser). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and serine. This variant is present in population databases (rs1800086, ExAC 0.03%). This variant has been reported in individuals with pancreatitis, congenital absence of the vas deferens (CAVD), and mild or atypical cysitic fibrosis (PMID: 2395135, 9272157, 16128988, 23670503, 15858154). However, a pathogenic variant was observed on the opposite allele in only one of these individuals (PMID: 9272157), and in that report only a small number of common mutations were tested. As a result, it is uncertain if this c.1052C>G variant contributes to disease in any of these affected individuals. ClinVar contains an entry for this variant (Variation ID: 53174). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant is a rare missense change with uncertain impact on protein function. It has been reported in both the population and affected individuals, but the available evidence is currently insufficient to determine its role 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

From Mendelics, SCV000886356.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownyesnot providednot providednot providednot providednot providednot providednot provided

From Nilou-Genome Lab, SCV001822034.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenonot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 27, 2021

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