NM_000260.4(MYO7A):c.999T>G (p.Tyr333Ter) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jan 30, 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:: RCV000421042.13

Allele description [Variation Report for NM_000260.4(MYO7A):c.999T>G (p.Tyr333Ter)]

NM_000260.4(MYO7A):c.999T>G (p.Tyr333Ter)

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.999T>G (p.Tyr333Ter)

HGVS:

NC_000011.10:g.77158426T>G
NG_009086.2:g.35181T>G
NM_000260.4:c.999T>GMANE SELECT
NM_001127180.2:c.999T>G
NM_001369365.1:c.966T>G
NP_000251.3:p.Tyr333Ter
NP_001120652.1:p.Tyr333Ter
NP_001356294.1:p.Tyr322Ter
LRG_1420t1:c.999T>G
LRG_1420:g.35181T>G
LRG_1420p1:p.Tyr333Ter
NC_000011.9:g.76869472T>G
NG_009086.1:g.35163T>G
NM_000260.3:c.999T>G
c.999T>G
p.Tyr333X

Protein change:

Y322*

Links:

dbSNP: rs111033285

NCBI 1000 Genomes Browser:

rs111033285

Molecular consequence:

NM_000260.4:c.999T>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001127180.2:c.999T>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001369365.1:c.966T>G - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Mus musculus cullin 1 (Cul1), mRNA
Mus musculus cullin 1 (Cul1), mRNA
gi|34328459|ref|NM_012042.3|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000521009	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jun 5, 2023)	germline	clinical testing	Citation Link,
SCV000854941	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL ClinVar v180209 classification definitions)	Pathogenic (Jul 24, 2018)	germline	clinical testing	Citation Link,
SCV001395944	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 30, 2024)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 25404053, 8900236, 26969326, 27344577, 30390570, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000521009

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Jun 5, 2023)

germline

clinical testing

Citation Link,

SCV000854941

Eurofins Ntd Llc (ga)

criteria provided, single submitter

(EGL ClinVar v180209 classification definitions)

Pathogenic
(Jul 24, 2018)

germline

clinical testing

Citation Link,

SCV001395944

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 30, 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	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Targeted next generation sequencing for molecular diagnosis of Usher syndrome.

Aparisi MJ, Aller E, Fuster-García C, García-García G, Rodrigo R, Vázquez-Manrique RP, Blanco-Kelly F, Ayuso C, Roux AF, Jaijo T, Millán JM.

Orphanet J Rare Dis. 2014 Nov 18;9:168. doi: 10.1186/s13023-014-0168-7.

PubMed [citation]

PMID:: 25404053
PMCID:: PMC4245769

Myosin VIIA mutation screening in 189 Usher syndrome type 1 patients.

Weston MD, Kelley PM, Overbeck LD, Wagenaar M, Orten DJ, Hasson T, Chen ZY, Corey D, Mooseker M, Sumegi J, Cremers C, Moller C, Jacobson SG, Gorin MB, Kimberling WJ.

Am J Hum Genet. 1996 Nov;59(5):1074-83.

PubMed [citation]

PMID:: 8900236
PMCID:: PMC1914835

See all PubMed Citations (6)

Details of each submission

From GeneDx, SCV000521009.7

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

Description

Nonsense 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; Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 16400615, 21873662, 27344577, 18463160, 26969326, 30390570, 21436283, 8900236, 32981126, 34948090, 34599368)

#	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 Eurofins Ntd Llc (ga), SCV000854941.1

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

#	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		1	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001395944.5

#	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.Tyr333*) in the MYO7A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MYO7A are known to be pathogenic (PMID: 8900236, 25404053). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with autosomal recessive MYO7A-related conditions (PMID: 8900236, 26969326, 27344577, 30390570). ClinVar contains an entry for this variant (Variation ID: 43345). 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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