NM_000260.4(MYO7A):c.2323C>T (p.Gln775Ter) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Sep 1, 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:: RCV001383210.7

Allele description [Variation Report for NM_000260.4(MYO7A):c.2323C>T (p.Gln775Ter)]

NM_000260.4(MYO7A):c.2323C>T (p.Gln775Ter)

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.2323C>T (p.Gln775Ter)

HGVS:

NC_000011.10:g.77179085C>T
NG_009086.2:g.55840C>T
NM_000260.4:c.2323C>TMANE SELECT
NM_001127180.2:c.2323C>T
NM_001369365.1:c.2290C>T
NP_000251.3:p.Gln775Ter
NP_001120652.1:p.Gln775Ter
NP_001356294.1:p.Gln764Ter
LRG_1420t1:c.2323C>T
LRG_1420:g.55840C>T
LRG_1420p1:p.Gln775Ter
NC_000011.9:g.76890131C>T
NG_009086.1:g.55822C>T
NM_000260.3:c.2323C>T
p.Gln775X

Protein change:

Q764*

Links:

dbSNP: rs201892914

NCBI 1000 Genomes Browser:

rs201892914

Molecular consequence:

NM_000260.4:c.2323C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001127180.2:c.2323C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001369365.1:c.2290C>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV001582290	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 1, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 8900236, 25404053, 26969326, 28492532
SCV003923828	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (May 4, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001582290

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 1, 2024)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV003923828

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(May 4, 2023)

germline

clinical testing

Citation Link

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

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

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

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001582290.5

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

Description

This sequence change creates a premature translational stop signal (p.Gln775*) 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). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with autosomal recessive Usher syndrome (PMID: 26969326). ClinVar contains an entry for this variant (Variation ID: 371700). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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

From GeneDx, SCV003923828.1

#	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 at a significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 16963483, 26969326)

#	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

Last Updated: Feb 25, 2025

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