NM_153676.4(USH1C):c.586C>T (p.Arg196Ter) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 30, 2023
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:: RCV001383895.6

Allele description [Variation Report for NM_153676.4(USH1C):c.586C>T (p.Arg196Ter)]

NM_153676.4(USH1C):c.586C>T (p.Arg196Ter)

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.586C>T (p.Arg196Ter)

HGVS:

NC_000011.10:g.17526435G>A
NG_011883.2:g.22982C>T
NM_001297764.2:c.586C>T
NM_005709.4:c.586C>T
NM_153676.4:c.586C>TMANE SELECT
NP_001284693.1:p.Arg196Ter
NP_005700.2:p.Arg196Ter
NP_710142.1:p.Arg196Ter
NC_000011.9:g.17547982G>A
NR_123738.2:n.695C>T

Protein change:

R196*

Links:

dbSNP: rs1290295453

NCBI 1000 Genomes Browser:

rs1290295453

Molecular consequence:

NR_123738.2:n.695C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001297764.2:c.586C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_005709.4:c.586C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_153676.4:c.586C>T - 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
SCV001583218	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 30, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 27460420, 27848944, 10973247, 17407589, 20301442, 21203349, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001583218

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 30, 2023)

germline

clinical testing

PubMed (7)
[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

An innovative strategy for the molecular diagnosis of Usher syndrome identifies causal biallelic mutations in 93% of European patients.

Bonnet C, Riahi Z, Chantot-Bastaraud S, Smagghe L, Letexier M, Marcaillou C, Lefèvre GM, Hardelin JP, El-Amraoui A, Singh-Estivalet A, Mohand-Saïd S, Kohl S, Kurtenbach A, Sliesoraityte I, Zobor D, Gherbi S, Testa F, Simonelli F, Banfi S, Fakin A, Glavač D, Jarc-Vidmar M, et al.

Eur J Hum Genet. 2016 Dec;24(12):1730-1738. doi: 10.1038/ejhg.2016.99. Epub 2016 Jul 27.

PubMed [citation]

PMID:: 27460420
PMCID:: PMC5117943

Clinical exome sequencing: results from 2819 samples reflecting 1000 families.

Trujillano D, Bertoli-Avella AM, Kumar Kandaswamy K, Weiss ME, Köster J, Marais A, Paknia O, Schröder R, Garcia-Aznar JM, Werber M, Brandau O, Calvo Del Castillo M, Baldi C, Wessel K, Kishore S, Nahavandi N, Eyaid W, Al Rifai MT, Al-Rumayyan A, Al-Twaijri W, Alothaim A, Alhashem A, et al.

Eur J Hum Genet. 2017 Feb;25(2):176-182. doi: 10.1038/ejhg.2016.146. Epub 2016 Nov 16.

PubMed [citation]

PMID:: 27848944
PMCID:: PMC5255946

See all PubMed Citations (7)

Details of each submission

From Invitae, SCV001583218.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1031570). This premature translational stop signal has been observed in individual(s) with clinical features of USH1C-related conditions (PMID: 27460420, 27848944). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Arg196*) 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).

#	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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