NM_016239.4(MYO15A):c.4252G>A (p.Gly1418Arg) AND Rare genetic deafness

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jun 19, 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:: RCV001449688.5

Allele description [Variation Report for NM_016239.4(MYO15A):c.4252G>A (p.Gly1418Arg)]

NM_016239.4(MYO15A):c.4252G>A (p.Gly1418Arg)

Gene:

MYO15A:myosin XVA [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17p11.2

Genomic location:

Preferred name:

NM_016239.4(MYO15A):c.4252G>A (p.Gly1418Arg)

HGVS:

NC_000017.11:g.18132498G>A
NG_011634.2:g.28793G>A
NM_016239.4:c.4252G>AMANE SELECT
NP_057323.3:p.Gly1418Arg
NC_000017.10:g.18035812G>A
NM_016239.3:c.4252G>A

Protein change:

G1418R

Links:

dbSNP: rs753790346

Molecular consequence:

NM_016239.4:c.4252G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Rare genetic deafness
Identifiers:: MedGen: C5680250; Orphanet: 96210

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001652940	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely Pathogenic (Jun 19, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 30953472, 25373420, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001652940

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely Pathogenic
(Jun 19, 2023)

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

Genotype-phenotype correlation analysis of MYO15A variants in autosomal recessive non-syndromic hearing loss.

Zhang J, Guan J, Wang H, Yin L, Wang D, Zhao L, Zhou H, Wang Q.

BMC Med Genet. 2019 Apr 5;20(1):60. doi: 10.1186/s12881-019-0790-2.

PubMed [citation]

PMID:: 30953472
PMCID:: PMC6451310

Exploration of molecular genetic etiology for Korean cochlear implantees with severe to profound hearing loss and its implication.

Park JH, Kim NK, Kim AR, Rhee J, Oh SH, Koo JW, Nam JY, Park WY, Choi BY.

Orphanet J Rare Dis. 2014 Nov 6;9:167. doi: 10.1186/s13023-014-0167-8.

PubMed [citation]

PMID:: 25373420
PMCID:: PMC4243193

See all PubMed Citations (3)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV001652940.2

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

Description

The p.Gly1418Arg variant in MYO15A has been previously reported in three compound heterozygous individuals with congenital profound hearing loss (Park 2014 PMID: 25373420, Zhang 2019 PMID: 30953472, LMM internal data). This variant has been identified in 0.0065% (1/15280) of Latino chromosomes by gnomAD (http://gnomad.broadinstitute.org, v.3.1.2); however, this frequency is low enough to be consistent with a recessive allele frequency. Computational prediction tools and conservation analysis suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal recessive hearing loss. ACMG/AMP Criteria applied: PM3_Strong, PM2_Supporting, PP3.

#	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: Apr 12, 2026

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