NM_017433.5(MYO3A):c.315del (p.Gly106fs) AND not provided

Germline classification:: Conflicting classifications of pathogenicity (2 submissions)
Last evaluated:: Sep 25, 2023
Review status:: criteria provided, conflicting classifications

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:: RCV001799672.8

Allele description [Variation Report for NM_017433.5(MYO3A):c.315del (p.Gly106fs)]

NM_017433.5(MYO3A):c.315del (p.Gly106fs)

Gene:

MYO3A:myosin IIIA [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

10p12.1

Genomic location:

Preferred name:

NM_017433.5(MYO3A):c.315del (p.Gly106fs)

HGVS:

NC_000010.11:g.25996501del
NG_011635.1:g.67429del
NM_001368265.1:c.315del
NM_017433.5:c.315delMANE SELECT
NP_001355194.1:p.Gly106fs
NP_059129.3:p.Gly106fs
LRG_1354t1:c.315del
LRG_1354:g.67429del
LRG_1354p1:p.Gly106fs
NC_000010.10:g.26285430del
NC_000010.11:g.25996501delA
NM_017433.4:c.315del

Protein change:

G106fs

Links:

dbSNP: rs777580042

NCBI 1000 Genomes Browser:

rs777580042

Molecular consequence:

NM_001368265.1:c.315del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_017433.5:c.315del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002043833	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Jun 21, 2021)	germline	clinical testing	Citation Link,
SCV002125449	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 25, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 12032315, 23990876, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002043833

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Jun 21, 2021)

germline

clinical testing

Citation Link,

SCV002125449

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 25, 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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

From flies' eyes to our ears: mutations in a human class III myosin cause progressive nonsyndromic hearing loss DFNB30.

Walsh T, Walsh V, Vreugde S, Hertzano R, Shahin H, Haika S, Lee MK, Kanaan M, King MC, Avraham KB.

Proc Natl Acad Sci U S A. 2002 May 28;99(11):7518-23.

PubMed [citation]

PMID:: 12032315
PMCID:: PMC124268

Diagnostic application of targeted resequencing for familial nonsyndromic hearing loss.

Choi BY, Park G, Gim J, Kim AR, Kim BJ, Kim HS, Park JH, Park T, Oh SH, Han KH, Park WY.

PLoS One. 2013;8(8):e68692. doi: 10.1371/journal.pone.0068692.

PubMed [citation]

PMID:: 23990876
PMCID:: PMC3750053

See all PubMed Citations (3)

Details of each submission

From GeneDx, SCV002043833.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27535533, 31589614)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002125449.3

#	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 creates a premature translational stop signal (p.Gly106Aspfs*3) in the MYO3A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MYO3A are known to be pathogenic (PMID: 12032315, 23990876). This variant is present in population databases (rs777580042, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with MYO3A-related conditions. ClinVar contains an entry for this variant (Variation ID: 439958). 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: Jan 19, 2025

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