NM_153676.4(USH1C):c.1016G>A (p.Arg339Gln) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 31, 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:: RCV002532049.1

Allele description [Variation Report for NM_153676.4(USH1C):c.1016G>A (p.Arg339Gln)]

NM_153676.4(USH1C):c.1016G>A (p.Arg339Gln)

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.1016G>A (p.Arg339Gln)

HGVS:

NC_000011.10:g.17522787C>T
NG_011883.2:g.26630G>A
NM_001297764.2:c.959G>A
NM_005709.4:c.1016G>A
NM_153676.4:c.1016G>AMANE SELECT
NP_001284693.1:p.Arg320Gln
NP_005700.2:p.Arg339Gln
NP_710142.1:p.Arg339Gln
NC_000011.9:g.17544334C>T
NG_011883.1:g.26630G>A
NM_005709.3:c.1016G>A
NR_123738.2:n.1125G>A

Protein change:

R320Q

Links:

dbSNP: rs765571023

NCBI 1000 Genomes Browser:

rs765571023

Molecular consequence:

NM_001297764.2:c.959G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_005709.4:c.1016G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_153676.4:c.1016G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_123738.2:n.1125G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: CN517202

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003439586	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 31, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 22135276, 25788563, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003439586

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 31, 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

Citations

PubMed

Comprehensive sequence analysis of nine Usher syndrome genes in the UK National Collaborative Usher Study.

Le Quesne Stabej P, Saihan Z, Rangesh N, Steele-Stallard HB, Ambrose J, Coffey A, Emmerson J, Haralambous E, Hughes Y, Steel KP, Luxon LM, Webster AR, Bitner-Glindzicz M.

J Med Genet. 2012 Jan;49(1):27-36. doi: 10.1136/jmedgenet-2011-100468. Epub 2011 Dec 1.

PubMed [citation]

PMID:: 22135276
PMCID:: PMC3678402

Deafness gene variations in a 1120 nonsyndromic hearing loss cohort: molecular epidemiology and deafness mutation spectrum of patients in Japan.

Nishio SY, Usami S.

Ann Otol Rhinol Laryngol. 2015 May;124 Suppl 1:49S-60S. doi: 10.1177/0003489415575059. Epub 2015 Mar 18.

PubMed [citation]

PMID:: 25788563

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV003439586.1

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

Description

This sequence change replaces arginine with glutamine at codon 339 of the USH1C protein (p.Arg339Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs765571023, ExAC 0.006%). This missense change has been observed in individual(s) with clinical features of UH1C-related conditions (PMID: 22135276, 25788563). ClinVar contains an entry for this variant (Variation ID: 551086). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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 7, 2023

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