NM_007272.3(CTRC):c.760C>T (p.Arg254Trp) AND Inborn genetic diseases

Clinical significance:Pathogenic (Last evaluated: Mar 6, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001026619.1

Allele description [Variation Report for NM_007272.3(CTRC):c.760C>T (p.Arg254Trp)]

NM_007272.3(CTRC):c.760C>T (p.Arg254Trp)

Gene:
CTRC:chymotrypsin C [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1p36.21
Genomic location:
Preferred name:
NM_007272.3(CTRC):c.760C>T (p.Arg254Trp)
HGVS:
  • NC_000001.11:g.15445717C>T
  • NG_009253.1:g.12275C>T
  • NM_007272.3:c.760C>TMANE SELECT
  • NP_009203.2:p.Arg254Trp
  • NP_009203.2:p.Arg254Trp
  • NC_000001.10:g.15772212C>T
  • NM_007272.2:c.760C>T
  • Q99895:p.Arg254Trp
Protein change:
R254W; ARG254TRP
Links:
UniProtKB: Q99895#VAR_043529; OMIM: 601405.0001; dbSNP: rs121909293
NCBI 1000 Genomes Browser:
rs121909293
Molecular consequence:
  • NM_007272.3:c.760C>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Inborn genetic diseases
Identifiers:
MeSH: D030342; MedGen: C0950123

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001189039Ambry Geneticscriteria provided, single submitter
Pathogenic
(Mar 6, 2019)
germlineclinical testing

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

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Citations

PubMed

Comprehensive functional analysis of chymotrypsin C (CTRC) variants reveals distinct loss-of-function mechanisms associated with pancreatitis risk.

Beer S, Zhou J, Szabó A, Keiles S, Chandak GR, Witt H, Sahin-Tóth M.

Gut. 2013 Nov;62(11):1616-24. doi: 10.1136/gutjnl-2012-303090. Epub 2012 Sep 1.

PubMed [citation]
PMID:
22942235
PMCID:
PMC3660471

Details of each submission

From Ambry Genetics, SCV001189039.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

The p.R254W pathogenic mutation (also known as c.760C>T), located in coding exon 7 of the CTRC gene, results from a C to T substitution at nucleotide position 760. The arginine at codon 254 is replaced by tryptophan, an amino acid with dissimilar properties. This mutation has been shown to be over-represented in individuals with idiopathic or hereditary chronic pancreatitis; it was demonstrated to cause a reduction in chymotrypsin C activity due to decreased production and/or secretion (Rosendahl J et al. Nat Genet. 2008;40(1):78-82). <span style="background-color:initial">Another study found this mutation in 2.07% of affected individuals versus 0.57% of control individuals and in vitro<span style="background-color:initial"> studies suggest that this mutation results in slightly decreased protein secretion and increased rate of degradation by trypsin (Beer S et al. Gut<span style="background-color:initial">. 2013 Nov;62(11):1616-24). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

Last Updated: Oct 16, 2021

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