NM_153676.4(USH1C):c.1039C>T (p.Gln347Ter) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Jan 24, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000598390.9

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]

Observations:

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
SCV000706342	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Likely pathogenic (Feb 8, 2017)	germline	clinical testing	Citation Link,
SCV001585913	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 24, 2024)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 10973247, 17407589, 20301442, 21203349, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000706342

Eurofins Ntd Llc (ga)

criteria provided, single submitter

(EGL Classification Definitions 2015)

Likely pathogenic
(Feb 8, 2017)

germline

clinical testing

Citation Link,

SCV001585913

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 24, 2024)

germline

clinical testing

PubMed (5)
[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	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A defect in harmonin, a PDZ domain-containing protein expressed in the inner ear sensory hair cells, underlies Usher syndrome type 1C.

Verpy E, Leibovici M, Zwaenepoel I, Liu XZ, Gal A, Salem N, Mansour A, Blanchard S, Kobayashi I, Keats BJ, Slim R, Petit C.

Nat Genet. 2000 Sep;26(1):51-5.

PubMed [citation]

PMID:: 10973247

Deafblindness in French Canadians from Quebec: a predominant founder mutation in the USH1C gene provides the first genetic link with the Acadian population.

Ebermann I, Lopez I, Bitner-Glindzicz M, Brown C, Koenekoop RK, Bolz HJ.

Genome Biol. 2007;8(4):R47.

PubMed [citation]

PMID:: 17407589
PMCID:: PMC1895989

See all PubMed Citations (5)

Details of each submission

From Eurofins Ntd Llc (ga), SCV000706342.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	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	germline	unknown	not provided	not provided	not provided		1	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001585913.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change creates a premature translational stop signal (p.Gln347*) in the USH1C gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in USH1C are known to be pathogenic (PMID: 10973247, 17407589, 20301442, 21203349). This variant is present in population databases (rs762551629, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with USH1C-related conditions. ClinVar contains an entry for this variant (Variation ID: 500413). For these reasons, this variant has been classified as Pathogenic.

#	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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