NM_007272.3(CTRC):c.641G>A (p.Gly214Glu) AND Hereditary pancreatitis

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Aug 9, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001057575.10

Allele description [Variation Report for NM_007272.3(CTRC):c.641G>A (p.Gly214Glu)]

NM_007272.3(CTRC):c.641G>A (p.Gly214Glu)

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.641G>A (p.Gly214Glu)

HGVS:

NC_000001.11:g.15445598G>A
NG_009253.1:g.12156G>A
NM_007272.3:c.641G>AMANE SELECT
NP_009203.2:p.Gly214Glu
NC_000001.10:g.15772093G>A
NM_007272.2:c.641G>A

Protein change:

G214E

Links:

dbSNP: rs1013133526

NCBI 1000 Genomes Browser:

rs1013133526

Molecular consequence:

NM_007272.3:c.641G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary pancreatitis (PCTT)
Synonyms:: Hereditary chronic pancreatitis
Identifiers:: MONDO: MONDO:0008185; MedGen: C0238339; Orphanet: 676; OMIM: 167800

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001222074	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 9, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30420730, 28492532
SCV002661235	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Apr 15, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001222074

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 9, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV002661235

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Apr 15, 2021)

germline

clinical testing

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

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

SPINK1, PRSS1, CTRC, and CFTR Genotypes Influence Disease Onset and Clinical Outcomes in Chronic Pancreatitis.

Zou WB, Tang XY, Zhou DZ, Qian YY, Hu LH, Yu FF, Yu D, Wu H, Deng SJ, Lin JH, Zhao AJ, Zhao ZH, Wu HY, Zhu JH, Qian W, Wang L, Xin L, Wang MJ, Wang LJ, Fang X, He L, Masson E, et al.

Clin Transl Gastroenterol. 2018 Nov 12;9(11):204. doi: 10.1038/s41424-018-0069-5.

PubMed [citation]

PMID:: 30420730
PMCID:: PMC6232107

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001222074.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 214 of the CTRC protein (p.Gly214Glu). This variant is present in population databases (no rsID available, gnomAD 0.006%). This missense change has been observed in individual(s) with idiopathic chromic pancreatitis (PMID: 30420730). ClinVar contains an entry for this variant (Variation ID: 852868). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Ambry Genetics, SCV002661235.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

The p.G214E variant (also known as c.641G>A), located in coding exon 7 of the CTRC gene, results from a G to A substitution at nucleotide position 641. The glycine at codon 214 is replaced by glutamic acid, an amino acid with similar properties. This alteration was identified in 1/1061 individuals with chronic pancreatitis and in 0/1196 controls (Zou WB et al. Clin Transl Gastroenterol, 2018 11;9:204). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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