NM_001287.6(CLCN7):c.381G>A (p.Trp127Ter) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 26, 2022
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:: RCV002858255.3

Allele description [Variation Report for NM_001287.6(CLCN7):c.381G>A (p.Trp127Ter)]

NM_001287.6(CLCN7):c.381G>A (p.Trp127Ter)

Gene:

CLCN7:chloride voltage-gated channel 7 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16p13.3

Genomic location:

Preferred name:

NM_001287.6(CLCN7):c.381G>A (p.Trp127Ter)

HGVS:

NC_000016.10:g.1460919C>T
NG_007567.1:g.19166G>A
NM_001114331.3:c.309G>A
NM_001287.6:c.381G>AMANE SELECT
NP_001107803.1:p.Trp103Ter
NP_001278.1:p.Trp127Ter
NC_000016.9:g.1510920C>T

Protein change:

W103*

Molecular consequence:

NM_001114331.3:c.309G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001287.6:c.381G>A - nonsense - [Sequence Ontology: SO:0001587]

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
SCV003234801	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 26, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 14584882, 19953639, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003234801

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 26, 2022)

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

Chloride channel ClCN7 mutations are responsible for severe recessive, dominant, and intermediate osteopetrosis.

Frattini A, Pangrazio A, Susani L, Sobacchi C, Mirolo M, Abinun M, Andolina M, Flanagan A, Horwitz EM, Mihci E, Notarangelo LD, Ramenghi U, Teti A, Van Hove J, Vujic D, Young T, Albertini A, Orchard PJ, Vezzoni P, Villa A.

J Bone Miner Res. 2003 Oct;18(10):1740-7.

PubMed [citation]

PMID:: 14584882

Molecular and clinical heterogeneity in CLCN7-dependent osteopetrosis: report of 20 novel mutations.

Pangrazio A, Pusch M, Caldana E, Frattini A, Lanino E, Tamhankar PM, Phadke S, Lopez AG, Orchard P, Mihci E, Abinun M, Wright M, Vettenranta K, Bariae I, Melis D, Tezcan I, Baumann C, Locatelli F, Zecca M, Horwitz E, Mansour LS, Van Roij M, et al.

Hum Mutat. 2010 Jan;31(1):E1071-80. doi: 10.1002/humu.21167.

PubMed [citation]

PMID:: 19953639

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003234801.2

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with CLCN7-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp127*) in the CLCN7 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CLCN7 are known to be pathogenic (PMID: 14584882, 19953639).

#	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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