NM_004999.4(MYO6):c.1159C>T (p.Arg387Ter) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Jan 26, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000760878.4

Allele description [Variation Report for NM_004999.4(MYO6):c.1159C>T (p.Arg387Ter)]

NM_004999.4(MYO6):c.1159C>T (p.Arg387Ter)

Gene:

MYO6:myosin VI [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6q14.1

Genomic location:

Preferred name:

NM_004999.4(MYO6):c.1159C>T (p.Arg387Ter)

HGVS:

NC_000006.12:g.75855219C>T
NG_009934.2:g.111027C>T
NM_001300899.2:c.1159C>T
NM_001368136.1:c.1159C>T
NM_001368137.1:c.1159C>T
NM_001368138.1:c.1144C>T
NM_001368865.1:c.1159C>T
NM_001368866.1:c.1159C>T
NM_004999.4:c.1159C>TMANE SELECT
NP_001287828.1:p.Arg387Ter
NP_001355065.1:p.Arg387Ter
NP_001355066.1:p.Arg387Ter
NP_001355067.1:p.Arg382Ter
NP_001355794.1:p.Arg387Ter
NP_001355795.1:p.Arg387Ter
NP_004990.3:p.Arg387Ter
LRG_438t1:c.1159C>T
LRG_438:g.111027C>T
LRG_438p1:p.Arg387Ter
NC_000006.11:g.76564936C>T
NG_009934.1:g.111028C>T
NM_004999.3:c.1159C>T
NR_160538.1:n.1391C>T

Protein change:

R382*

Links:

dbSNP: rs766700803

NCBI 1000 Genomes Browser:

rs766700803

Molecular consequence:

NR_160538.1:n.1391C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001300899.2:c.1159C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001368136.1:c.1159C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001368137.1:c.1159C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001368138.1:c.1144C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001368865.1:c.1159C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001368866.1:c.1159C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_004999.4:c.1159C>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV000890774	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Likely pathogenic (Dec 13, 2018)	germline	clinical testing	Citation Link,
SCV002956011	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 26, 2024)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 12687499, 18348273, 23767834, 25999546, 30582396, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000890774

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Likely pathogenic
(Dec 13, 2018)

germline

clinical testing

Citation Link,

SCV002956011

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 26, 2024)

germline

clinical testing

PubMed (6)
[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

Mutations of MYO6 are associated with recessive deafness, DFNB37.

Ahmed ZM, Morell RJ, Riazuddin S, Gropman A, Shaukat S, Ahmad MM, Mohiddin SA, Fananapazir L, Caruso RC, Husnain T, Khan SN, Riazuddin S, Griffith AJ, Friedman TB, Wilcox ER.

Am J Hum Genet. 2003 May;72(5):1315-22. Epub 2003 Apr 8.

PubMed [citation]

PMID:: 12687499
PMCID:: PMC1180285

A novel nonsense mutation in MYO6 is associated with progressive nonsyndromic hearing loss in a Danish DFNA22 family.

Sanggaard KM, Kjaer KW, Eiberg H, Nürnberg G, Nürnberg P, Hoffman K, Jensen H, Sørum C, Rendtorff ND, Tranebjaerg L.

Am J Med Genet A. 2008 Apr 15;146A(8):1017-25. doi: 10.1002/ajmg.a.32174.

PubMed [citation]

PMID:: 18348273

See all PubMed Citations (6)

Details of each submission

From GeneDx, SCV000890774.1

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

Description

The R387X variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The variant is not observed in large population cohorts (Lek et al., 2016). It is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. We consider this variant to be likely pathogenic.

#	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, SCV002956011.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change creates a premature translational stop signal (p.Arg387*) in the MYO6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MYO6 are known to be pathogenic (PMID: 12687499, 18348273, 23767834, 25999546, 30582396). This variant is present in population databases (rs766700803, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with MYO6-related conditions. ClinVar contains an entry for this variant (Variation ID: 620495). 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: Sep 29, 2024

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