NM_000492.4(CFTR):c.407T>C (p.Leu136Pro) AND Cystic fibrosis

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 24, 2021
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:: RCV001047415.7

Allele description [Variation Report for NM_000492.4(CFTR):c.407T>C (p.Leu136Pro)]

NM_000492.4(CFTR):c.407T>C (p.Leu136Pro)

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.407T>C (p.Leu136Pro)

HGVS:

NC_000007.14:g.117531032T>C
NG_016465.4:g.70249T>C
NM_000492.4:c.407T>CMANE SELECT
NP_000483.3:p.Leu136Pro
LRG_663t1:c.407T>C
LRG_663:g.70249T>C
NC_000007.13:g.117171086T>C
NM_000492.3:c.407T>C

Protein change:

L136P

Links:

dbSNP: rs1798854681

NCBI 1000 Genomes Browser:

rs1798854681

Molecular consequence:

NM_000492.4:c.407T>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

Clear Turn Off Turn On

TESMIN testis expressed metallothionein like protein [Homo sapiens]
TESMIN testis expressed metallothionein like protein [Homo sapiens]
Gene ID:9633

Gene
9633[uid] AND (alive[prop]) (1)
Gene

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001211373	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 24, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 11119745, 23810505, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001211373

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 24, 2021)

germline

clinical testing

PubMed (3)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Congenital bilateral absence of the vas deferens: clinical characteristics, biological parameters, cystic fibrosis transmembrane conductance regulator gene mutations, and implications for genetic counseling.

Daudin M, Bieth E, Bujan L, Massat G, Pontonnier F, Mieusset R.

Fertil Steril. 2000 Dec;74(6):1164-74.

PubMed [citation]

PMID:: 11119745

Novel CFTR variants identified during the first 3 years of cystic fibrosis newborn screening in California.

Prach L, Koepke R, Kharrazi M, Keiles S, Salinas DB, Reyes MC, Pian M, Opsimos H, Otsuka KN, Hardy KA, Milla CE, Zirbes JM, Chipps B, O'Bra S, Saeed MM, Sudhakar R, Lehto S, Nielson D, Shay GF, Seastrand M, Jhawar S, Nickerson B, et al.

J Mol Diagn. 2013 Sep;15(5):710-22. doi: 10.1016/j.jmoldx.2013.05.006. Epub 2013 Jun 28.

PubMed [citation]

PMID:: 23810505
PMCID:: PMC5707181

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001211373.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces leucine with proline at codon 136 of the CFTR protein (p.Leu136Pro). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and proline. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individuals with cystic fibrosis (PMID: 11119745, 23810505). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine