NM_000260.4(MYO7A):c.3719G>A (p.Arg1240Gln) AND not provided

Germline classification:: Pathogenic (6 submissions)
Last evaluated:: Jan 13, 2025
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:: RCV000256123.46

Allele description [Variation Report for NM_000260.4(MYO7A):c.3719G>A (p.Arg1240Gln)]

NM_000260.4(MYO7A):c.3719G>A (p.Arg1240Gln)

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.3719G>A (p.Arg1240Gln)

HGVS:

NC_000011.10:g.77190108G>A
NG_009086.2:g.66863G>A
NM_000260.4:c.3719G>AMANE SELECT
NM_001127180.2:c.3719G>A
NM_001369365.1:c.3686G>A
NP_000251.3:p.Arg1240Gln
NP_000251.3:p.Arg1240Gln
NP_001120652.1:p.Arg1240Gln
NP_001356294.1:p.Arg1229Gln
LRG_1420t1:c.3719G>A
LRG_1420:g.66863G>A
LRG_1420p1:p.Arg1240Gln
NC_000011.9:g.76901153G>A
NG_009086.1:g.66844G>A
NM_000260.3:c.3719G>A
Q13402:p.Arg1240Gln
c.3719G>A

Protein change:

R1229Q

Links:

UniProtKB: Q13402#VAR_009337; dbSNP: rs111033178

NCBI 1000 Genomes Browser:

rs111033178

Molecular consequence:

NM_000260.4:c.3719G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127180.2:c.3719G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001369365.1:c.3686G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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
SCV000321919	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jun 19, 2020)	germline	clinical testing	Citation Link,
SCV000608608	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (May 1, 2023)	germline	clinical testing	Citation Link,
SCV000955876	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 13, 2025)	germline	clinical testing	PubMed (11) [See all records that cite these PMIDs] 10930322, 15043528, 16652077, 17361009, 18463160, 20513143, 21569298, 21873662, 22135276, 24199935, 28492532
SCV001923520	Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV001954855	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV001975636	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	5	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

Evaluation of the myosin VIIA gene and visual function in patients with Usher syndrome type I.

Bharadwaj AK, Kasztejna JP, Huq S, Berson EL, Dryja TP.

Exp Eye Res. 2000 Aug;71(2):173-81.

PubMed [citation]

PMID:: 10930322

Evaluation of visual impairment in Usher syndrome 1b and Usher syndrome 2a.

Pennings RJ, Huygen PL, Orten DJ, Wagenaar M, van Aarem A, Kremer H, Kimberling WJ, Cremers CW, Deutman AF.

Acta Ophthalmol Scand. 2004 Apr;82(2):131-9.

PubMed [citation]

PMID:: 15043528

See all PubMed Citations (11)

Details of each submission

From GeneDx, SCV000321919.8

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

Description

In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 18463160, 16679490, 20513143, 21436283, 19683999, 25468891, 16652077, 16400615, 17361009, 27068579, 28559085, 10094549, 10930322, 15043528, 21569298, 16963483, 26969326, 22135276, 15221449, 9354784, 28041643, 31479088, 31980526, 32581362, 31589614, 32467589, 33576794, 33576163, 10612833)

#	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 CeGaT Center for Human Genetics Tuebingen, SCV000608608.33

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	5	not provided	not provided	clinical testing	not provided

Description

MYO7A: PM3:Very Strong, PM2, PM5, PP1, PP3

#	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		5	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000955876.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (11)

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1240 of the MYO7A protein (p.Arg1240Gln). This variant is present in population databases (rs111033178, gnomAD 0.01%). This missense change has been observed in individual(s) with Usher syndrome (PMID: 10930322, 15043528, 16652077, 17361009, 18463160, 20513143, 21569298, 21873662, 22135276). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 43218). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt MYO7A protein function with a positive predictive value of 95%. This variant disrupts the p.Arg1240 amino acid residue in MYO7A. Other variant(s) that disrupt this residue have been observed in individuals with MYO7A-related conditions (PMID: 24199935), which suggests that this may be a clinically significant amino acid residue. 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 Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus, SCV001923520.1

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

From Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus, SCV001954855.1

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

From Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus, SCV001975636.1

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

Last Updated: Mar 22, 2025

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