NM_000260.4(MYO7A):c.2005C>T (p.Arg669Ter) AND Rare genetic deafness

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 22, 2013
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:: RCV000844716.5

Allele description [Variation Report for NM_000260.4(MYO7A):c.2005C>T (p.Arg669Ter)]

NM_000260.4(MYO7A):c.2005C>T (p.Arg669Ter)

Gene:

MYO7A:myosin VIIA [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q13.5

Genomic location:

Preferred name:

NM_000260.4(MYO7A):c.2005C>T (p.Arg669Ter)

HGVS:

NC_000011.10:g.77174825C>T
NG_009086.2:g.51580C>T
NM_000260.4:c.2005C>TMANE SELECT
NM_001127180.2:c.2005C>T
NM_001369365.1:c.1972C>T
NP_000251.3:p.Arg669Ter
NP_001120652.1:p.Arg669Ter
NP_001356294.1:p.Arg658Ter
LRG_1420t1:c.2005C>T
LRG_1420:g.51580C>T
LRG_1420p1:p.Arg669Ter
NC_000011.9:g.76885871C>T
NG_009086.1:g.51562C>T
NM_000260.3:c.2005C>T
c.2005C>T
p.Arg669X

Protein change:

R658*

Links:

dbSNP: rs111033201

NCBI 1000 Genomes Browser:

rs111033201

Molecular consequence:

NM_000260.4:c.2005C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001127180.2:c.2005C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001369365.1:c.1972C>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

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
SCV000059725	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Pathogenic (Nov 22, 2013)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 9718356, 21569298, 21436283, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000059725

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Pathogenic
(Nov 22, 2013)

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	not provided	5	3	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in the myosin VIIA gene cause a wide phenotypic spectrum, including atypical Usher syndrome.

Liu XZ, Hope C, Walsh J, Newton V, Ke XM, Liang CY, Xu LR, Zhou JM, Trump D, Steel KP, Bundey S, Brown SD.

Am J Hum Genet. 1998 Sep;63(3):909-12. No abstract available.

PubMed [citation]

PMID:: 9718356
PMCID:: PMC1377414

Complete exon sequencing of all known Usher syndrome genes greatly improves molecular diagnosis.

Bonnet C, Grati M, Marlin S, Levilliers J, Hardelin JP, Parodi M, Niasme-Grare M, Zelenika D, Délépine M, Feldmann D, Jonard L, El-Amraoui A, Weil D, Delobel B, Vincent C, Dollfus H, Eliot MM, David A, Calais C, Vigneron J, Montaut-Verient B, Bonneau D, et al.

Orphanet J Rare Dis. 2011 May 11;6:21. doi: 10.1186/1750-1172-6-21.

PubMed [citation]

PMID:: 21569298
PMCID:: PMC3125325

See all PubMed Citations (4)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000059725.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	5	not provided	not provided	clinical testing	PubMed (4)

Description

The p.Arg669X variant in MYO7A has been previously reported in at least 4 indivi duals with Usher syndrome (Bonnet 2011, Roux 2011, LMM-unpublished data). It has also been identified in 0.003% (5/127112) of European chromosomes by gnomAD (ht tp://gnomad.broadinstitute.org), though this frequency in the general population is consistent with a recessive carrier frequency. This nonsense variant leads t o a premature termination codon at position 669, which is predicted to lead to a truncated or absent protein. In summary, this variant meets criteria to be clas sified as pathogenic for autosomal recessive Usher syndrome. ACMG/AMP criteria a pplied: PVS1, PM2, PM3.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		5	not provided	3	not provided

Last Updated: Mar 22, 2025

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