NM_144672.4(OTOA):c.1265G>T (p.Gly422Val) AND not provided

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jan 27, 2024
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:: RCV001954351.4

Allele description [Variation Report for NM_144672.4(OTOA):c.1265G>T (p.Gly422Val)]

NM_144672.4(OTOA):c.1265G>T (p.Gly422Val)

Gene:

OTOA:otoancorin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16p12.2

Genomic location:

Preferred name:

NM_144672.4(OTOA):c.1265G>T (p.Gly422Val)

HGVS:

NC_000016.10:g.21710048G>T
NG_012973.2:g.50916G>T
NM_001161683.2:c.1028G>T
NM_144672.4:c.1265G>TMANE SELECT
NM_170664.3:c.293G>T
NP_001155155.1:p.Gly343Val
NP_653273.3:p.Gly422Val
NP_733764.1:p.Gly98Val
NC_000016.9:g.21721369G>T
NM_144672.3:c.1265G>T

Protein change:

G343V

Links:

dbSNP: rs200689333

NCBI 1000 Genomes Browser:

rs200689333

Molecular consequence:

NM_001161683.2:c.1028G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_144672.4:c.1265G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_170664.3:c.293G>T - missense variant - [Sequence Ontology: SO:0001583]

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
SCV002245146	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jan 27, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 33597575, 34416374, 37114731, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002245146

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jan 27, 2024)

germline

clinical testing

PubMed (4)
[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

Molecular diagnosis of non-syndromic hearing loss patients using a stepwise approach.

Wang J, Xiang J, Chen L, Luo H, Xu X, Li N, Cui C, Xu J, Song N, Peng J, Peng Z.

Sci Rep. 2021 Feb 17;11(1):4036. doi: 10.1038/s41598-021-83493-6.

PubMed [citation]

PMID:: 33597575
PMCID:: PMC7889619

Family trio-based sequencing in 404 sporadic bilateral hearing loss patients discovers recessive and De novo genetic variants in multiple ways.

Guan J, Li J, Chen G, Shi T, Lan L, Wu X, Zhao C, Wang D, Wang H, Wang Q.

Eur J Med Genet. 2021 Oct;64(10):104311. doi: 10.1016/j.ejmg.2021.104311. Epub 2021 Aug 17.

PubMed [citation]

PMID:: 34416374

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002245146.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 422 of the OTOA protein (p.Gly422Val). This variant is present in population databases (rs200689333, gnomAD 0.06%). This missense change has been observed in individual(s) with deafness (PMID: 33597575, 34416374, 37114731). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1462794). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely 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: Sep 29, 2024

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