NM_153676.4(USH1C):c.1039C>T (p.Gln347Ter) AND Usher syndrome type 1C

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: May 6, 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:: RCV000984228.4

Allele description [Variation Report for NM_153676.4(USH1C):c.1039C>T (p.Gln347Ter)]

NM_153676.4(USH1C):c.1039C>T (p.Gln347Ter)

Gene:

USH1C:USH1 protein network component harmonin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11p15.1

Genomic location:

Preferred name:

NM_153676.4(USH1C):c.1039C>T (p.Gln347Ter)

HGVS:

NC_000011.10:g.17521392G>A
NG_011883.2:g.28025C>T
NM_001297764.2:c.982C>T
NM_005709.4:c.1039C>T
NM_153676.4:c.1039C>TMANE SELECT
NP_001284693.1:p.Gln328Ter
NP_005700.2:p.Gln347Ter
NP_710142.1:p.Gln347Ter
NC_000011.9:g.17542939G>A
NG_011883.1:g.28025C>T
NM_153676.3:c.1039C>T
NR_123738.2:n.1148C>T

Protein change:

Q328*

Links:

dbSNP: rs762551629

NCBI 1000 Genomes Browser:

rs762551629

Molecular consequence:

NR_123738.2:n.1148C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001297764.2:c.982C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_005709.4:c.1039C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_153676.4:c.1039C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Usher syndrome type 1C
Synonyms:: USHER SYNDROME, TYPE I, ACADIAN VARIETY; Usher syndrome, Acadian variety
Identifiers:: MONDO: MONDO:0010171; MedGen: C1848604; Orphanet: 231169; Orphanet: 886; OMIM: 276904

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001132304	Counsyl	no assertion criteria provided	Likely pathogenic (Jan 17, 2017)	unknown	clinical testing
SCV002557880	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 6, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 27957503, 31858762, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001132304

Counsyl

no assertion criteria provided

Likely pathogenic
(Jan 17, 2017)

unknown

clinical testing

SCV002557880

Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(May 6, 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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Usher syndrome in Denmark: mutation spectrum and some clinical observations.

Dad S, Rendtorff ND, Tranebjærg L, Grønskov K, Karstensen HG, Brox V, Nilssen Ø, Roux AF, Rosenberg T, Jensen H, Møller LB.

Mol Genet Genomic Med. 2016 Sep;4(5):527-539.

PubMed [citation]

PMID:: 27957503
PMCID:: PMC5023938

A Novel Heterozygous Missense Variant (c.667G>T;p.Gly223Cys) in USH1C That Interferes With Cadherin-Related 23 and Harmonin Interaction Causes Autosomal Dominant Nonsyndromic Hearing Loss.

Song JS, Bahloul A, Petit C, Kim SJ, Moon IJ, Lee J, Ki CS.

Ann Lab Med. 2020 May;40(3):224-231. doi: 10.3343/alm.2020.40.3.224.

PubMed [citation]

PMID:: 31858762
PMCID:: PMC6933062

See all PubMed Citations (3)

Details of each submission

From Counsyl, SCV001132304.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

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

From Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV002557880.2

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

Description

Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with autosomal recessive deafness 18A (MIM#602092) and Usher syndrome, type 1C (MIM#276904). Dominant negative is a suggested mechanism for rare autosomal dominant non-syndromic hearing loss (NSHL) (PMID: 31858762). (I) 0106 - This gene is associated with autosomal recessive disease. A single, large family with a heterozygous missense variant has been reported with autosomal dominant NSHL (PMID: 31858762). (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD (v2) <0.01 for a recessive condition (4 heterozygotes, 0 homozygotes). (SP) 0701 - Other NMD-predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. Many NMD-predicted variants have been reported as pathogenic, and are generally observed in patients with Usher syndrome (OMIM, PMID: 27957503). (SP) 0803 - This variant has limited previous evidence of pathogenicity in unrelated individuals. This variant has been reported several times as likely pathogenic (ClinVar), but also as a VUS due to insufficient information (deafnessvariationdatabase). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

#	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: Oct 13, 2024

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