NM_000492.4(CFTR):c.2900T>C (p.Leu967Ser) AND multiple conditions

Germline classification:: Conflicting classifications of pathogenicity (2 submissions)
Last evaluated:: Aug 7, 2024
Review status:: criteria provided, conflicting classifications

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:: RCV005031775.2

Allele description [Variation Report for NM_000492.4(CFTR):c.2900T>C (p.Leu967Ser)]

NM_000492.4(CFTR):c.2900T>C (p.Leu967Ser)

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.2900T>C (p.Leu967Ser)

HGVS:

NC_000007.14:g.117603774T>C
NG_016465.4:g.142991T>C
NM_000492.4:c.2900T>CMANE SELECT
NP_000483.3:p.Leu967Ser
NP_000483.3:p.Leu967Ser
LRG_663t1:c.2900T>C
LRG_663:g.142991T>C
LRG_663p1:p.Leu967Ser
NC_000007.13:g.117243828T>C
NM_000492.3:c.2900T>C
P13569:p.Leu967Ser

Protein change:

L967S

Links:

UniProtKB: P13569#VAR_009905; dbSNP: rs1800110

Molecular consequence:

NM_000492.4:c.2900T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Bronchiectasis with or without elevated sweat chloride 1 (BESC1)
Synonyms:: Cystic Fibrosis-Like Syndrome
Identifiers:: MONDO: MONDO:0008887; MedGen: C2749757; Orphanet: 60033; OMIM: 211400

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

Name:: Hereditary pancreatitis (PCTT)
Synonyms:: Hereditary chronic pancreatitis; PRSS1-Related Hereditary Pancreatitis
Identifiers:: MONDO: MONDO:0008185; MedGen: C0238339; Orphanet: 676; OMIM: 167800

Name:: Congenital bilateral aplasia of vas deferens from CFTR mutation (CBAVD)
Identifiers:: MONDO: MONDO:0010178; MedGen: C0403814; Orphanet: 48; OMIM: 277180

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000603067	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024)	Pathogenic (Aug 7, 2024)	germline	clinical testing	Citation Link,
SCV005666388	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jun 10, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000603067

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process 2024)

Pathogenic
(Aug 7, 2024)

germline

clinical testing

Citation Link,

SCV005666388

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jun 10, 2024)

germline

clinical testing

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

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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV000603067.5

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

Description

The CFTR c.2900T>C; p.Leu967Ser variant (rs1800110) is reported in the literature in multiple individuals affected with CFTR-related disorders, including some with a pathogenic variant in trans (Bishop 2005, Cohn 2005, Masson 2013, Wang 2000). This variant is observed at a higher frequency in individuals diagnosed with pancreatitis compared to unaffected individuals (odds ratio >5, p<0.05) (LaRusch 2014). The p.Leu967Ser variant is reported in ClinVar (Variation ID: 219537), and it is found in the general population with an overall allele frequency of 0.07% (199/282620 alleles) in the Genome Aggregation Database. Functional assays suggest this variant has a modest or no effect on chloride channel activity, but exhibits decreased bicarbonate transport (LaRusch 2014, Raraigh 2018). Based on available information, this variant is not expected to cause classic cystic fibrosis, but is considered to be pathogenic-mild for CFTR-related disorders. References: Bishop MD et al. The cystic fibrosis transmembrane conductance regulator gene and ion channel function in patients with idiopathic pancreatitis. Hum Genet. 2005 Dec;118(3-4):372-81. PMID: 16193325 Cohn JA et al. Increased risk of idiopathic chronic pancreatitis in cystic fibrosis carriers. Hum Mutat. 2005 Oct;26(4):303-7. PMID: 16134171 LaRusch J et al. Mechanisms of CFTR functional variants that impair regulated bicarbonate permeation and increase risk for pancreatitis but not for cystic fibrosis. PLoS Genet. 2014 10(7):e1004376. PMID: 25033378 Masson E et al. A conservative assessment of the major genetic causes of idiopathic chronic pancreatitis: data from a comprehensive analysis of PRSS1, SPINK1, CTRC and CFTR genes in 253 young French patients. PLoS One.2013 8(8):e73522. PMID: 23951356 Raraigh KS et al. Functional Assays Are Essential for Interpretation of Missense Variants Associated with Variable Expressivity. Am J Hum Genet. 2018 Jun 7;102(6):1062-1077. PMID: 29805046 Wang X et al. Mutation in the gene responsible for cystic fibrosis and predisposition to chronic rhinosinusitis in the general population. JAMA. 2000 Oct 11;284(14):1814-9. PMID: 11025834

#	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 Fulgent Genetics, Fulgent Genetics, SCV005666388.1

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

#	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: Jun 20, 2026

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