NM_033056.3(PCDH15):c.1927C>T (p.Arg643Ter) AND Usher syndrome, type 1F

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

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 10, 2014
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:: RCV000154331.1

Allele description

NM_033056.3(PCDH15):c.1927C>T (p.Arg643Ter)

Gene:

PCDH15:protocadherin related 15 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q21.1

Genomic location:

Preferred name:

NM_033056.3(PCDH15):c.1927C>T (p.Arg643Ter)

HGVS:

NC_000010.11:g.54090054G>A
NG_009191.3:g.1544129C>T
NM_001142765.1:c.1785-10630C>T
NM_033056.3:c.1927C>T
NP_149045.3:p.Arg643Ter
NC_000010.10:g.55849814G>A
p.Arg643X

Protein change:

R643*

Links:

dbSNP: rs727504301

NCBI 1000 Genomes Browser:

rs727504301

Molecular consequence:

NM_001142765.1:c.1785-10630C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_033056.3:c.1927C>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

Name:: Usher syndrome, type 1F (USH1F)
Synonyms:: USHER SYNDROME, TYPE IF
Identifiers:: MedGen: C1865885; Orphanet: 231169; Orphanet: 886; OMIM: 602083

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000203994	Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Pathogenic (Feb 10, 2014)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 14570705, 16679490, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000203994

Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Pathogenic
(Feb 10, 2014)

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	not provided	1	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

PCDH15 is expressed in the neurosensory epithelium of the eye and ear and mutant alleles are responsible for both USH1F and DFNB23.

Ahmed ZM, Riazuddin S, Ahmad J, Bernstein SL, Guo Y, Sabar MF, Sieving P, Riazuddin S, Griffith AJ, Friedman TB, Belyantseva IA, Wilcox ER.

Hum Mol Genet. 2003 Dec 15;12(24):3215-23. Epub 2003 Oct 21.

PubMed [citation]

PMID:: 14570705

Survey of the frequency of USH1 gene mutations in a cohort of Usher patients shows the importance of cadherin 23 and protocadherin 15 genes and establishes a detection rate of above 90%.

Roux AF, Faugère V, Le Guédard S, Pallares-Ruiz N, Vielle A, Chambert S, Marlin S, Hamel C, Gilbert B, Malcolm S, Claustres M; French Usher Syndrome Collaboration..

J Med Genet. 2006 Sep;43(9):763-8. Epub 2006 May 5.

PubMed [citation]

PMID:: 16679490
PMCID:: PMC2564578

See all PubMed Citations (3)

Details of each submission

From Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine, SCV000203994.4

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

Description

The Arg643X variant in PCDH15 has been reported in two individuals with Usher syndrome (Ahmed 2003, Roux 2006), and was not identified in large population studies. Both of these individuals were homozygous or compound heterozygous with a second pathogenic variant and this variant segregated in two affected siblings. This nonsense variant leads to a premature termination codon at position 643, which is predicted to lead to a truncated or absent protein. In summary, this variant meets our criteria to be classified as pathogenic (http://pcpgm.partners.org/LMM).

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

Last Updated: Mar 31, 2019

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