NM_000492.4(CFTR):c.305T>C (p.Leu102Pro) AND Cystic fibrosis

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Nov 21, 2020
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000577371.7

Allele description [Variation Report for NM_000492.4(CFTR):c.305T>C (p.Leu102Pro)]

NM_000492.4(CFTR):c.305T>C (p.Leu102Pro)

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.305T>C (p.Leu102Pro)

HGVS:

NC_000007.14:g.117530930T>C
NG_016465.4:g.70147T>C
NM_000492.4:c.305T>CMANE SELECT
NP_000483.3:p.Leu102Pro
NP_000483.3:p.Leu102Pro
LRG_663t1:c.305T>C
LRG_663:g.70147T>C
LRG_663p1:p.Leu102Pro
NC_000007.13:g.117170984T>C
NM_000492.3:c.305T>C

Protein change:

L102P

Links:

dbSNP: rs397508490

NCBI 1000 Genomes Browser:

rs397508490

Molecular consequence:

NM_000492.4:c.305T>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

Recent activity

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rhodopsin, partial [Apterichtus klazingai]
rhodopsin, partial [Apterichtus klazingai]
gi|1517359724|gb|AYW11981.1|

Protein
THI12 4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate synthase [Saccharomyc...
THI12 4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate synthase [Saccharomyces cerevisiae S288C]
Gene ID:855384

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000679427	ClinVar Staff, National Center for Biotechnology Information (NCBI)	no classification provided	not provided	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV002281112	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Nov 21, 2020)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 21708286, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000679427

ClinVar Staff, National Center for Biotechnology Information (NCBI)

no classification provided

not provided

germline

literature only

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

SCV002281112

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Nov 21, 2020)

germline

clinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Orphan missense mutations in the cystic fibrosis transmembrane conductance regulator: A three-step biological approach to establishing a correlation between genotype and phenotype.

Fresquet F, Clement R, Norez C, Sterlin A, Melin P, Becq F, Kitzis A, Thoreau V, Bilan F.

J Mol Diagn. 2011 Sep;13(5):520-7. doi: 10.1016/j.jmoldx.2011.05.004. Epub 2011 Jun 25.

PubMed [citation]

PMID:: 21708286
PMCID:: PMC3157621

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

Details of each submission

From ClinVar Staff, National Center for Biotechnology Information (NCBI), SCV000679427.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002281112.3

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

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies have shown that this variant affects CFTR protein function (PMID: 21708286). This variant has been observed in individual(s) with cystic fibrosis (PMID: 21708286). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 53642). This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with proline at codon 102 of the CFTR protein (p.Leu102Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline.

#	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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