NM_006580.4(CLDN16):c.224T>C (p.Leu75Pro) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 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:: RCV001851694.5

Allele description

NM_006580.4(CLDN16):c.224T>C (p.Leu75Pro)

Gene:

CLDN16:claudin 16 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3q28

Genomic location:

Preferred name:

NM_006580.4(CLDN16):c.224T>C (p.Leu75Pro)

Other names:

L145P

HGVS:

NC_000003.12:g.190404768T>C
NG_008149.1:g.21717T>C
NM_001378492.1:c.224T>C
NM_001378493.1:c.224T>C
NM_006580.4:c.224T>CMANE SELECT
NP_001365421.1:p.Leu75Pro
NP_001365422.1:p.Leu75Pro
NP_006571.2:p.Leu75Pro
NC_000003.11:g.190122557T>C
Q9Y5I7:p.Leu145Pro

Protein change:

L75P; LEU145PRO

Links:

UniProtKB: Q9Y5I7#VAR_017229; OMIM: 603959.0012; dbSNP: rs104893731

NCBI 1000 Genomes Browser:

rs104893731

Molecular consequence:

NM_001378492.1:c.224T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001378493.1:c.224T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_006580.4:c.224T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002236403	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 24, 2021)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16234325, 10878661, 18003771, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002236403

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 24, 2021)

germline

clinical testing

PubMed (4)
[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

Paracellin-1 and the modulation of ion selectivity of tight junctions.

Hou J, Paul DL, Goodenough DA.

J Cell Sci. 2005 Nov 1;118(Pt 21):5109-18. Epub 2005 Oct 18.

PubMed [citation]

PMID:: 16234325

Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis maps to chromosome 3q27 and is associated with mutations in the PCLN-1 gene.

Weber S, Hoffmann K, Jeck N, Saar K, Boeswald M, Kuwertz-Broeking E, Meij II, Knoers NV, Cochat P, Suláková T, Bonzel KE, Soergel M, Manz F, Schaerer K, Seyberth HW, Reis A, Konrad M.

Eur J Hum Genet. 2000 Jun;8(6):414-22.

PubMed [citation]

PMID:: 10878661

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV002236403.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this variant affects CLDN16 protein function (PMID: 16234325). This variant has been observed in individual(s) with familial hypomagnesemia with hypercalciuria and nephrocalcinosis (PMID: 10878661, 18003771, Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 5936). This variant is present in population databases (rs104893731, ExAC 0.001%). This sequence change replaces leucine with proline at codon 145 of the CLDN16 protein (p.Leu145Pro). 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: Feb 20, 2024

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