NM_000260.4(MYO7A):c.5618G>A (p.Arg1873Gln) AND not provided

Germline classification:: Conflicting classifications of pathogenicity (5 submissions)
Last evaluated:: Mar 25, 2025
Review status:: criteria provided, conflicting classifications

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:: RCV000594226.18

Allele description [Variation Report for NM_000260.4(MYO7A):c.5618G>A (p.Arg1873Gln)]

NM_000260.4(MYO7A):c.5618G>A (p.Arg1873Gln)

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.5618G>A (p.Arg1873Gln)

HGVS:

NC_000011.10:g.77205599G>A
NG_009086.2:g.82354G>A
NM_000260.4:c.5618G>AMANE SELECT
NM_001127180.2:c.5504G>A
NM_001369365.1:c.5471G>A
NP_000251.3:p.Arg1873Gln
NP_001120652.1:p.Arg1835Gln
NP_001356294.1:p.Arg1824Gln
LRG_1420t1:c.5618G>A
LRG_1420:g.82354G>A
LRG_1420p1:p.Arg1873Gln
NC_000011.9:g.76916644G>A
NG_009086.1:g.82335G>A
NM_000260.3:c.5618G>A
NM_000260.4(MYO7A):c.5618G>AMANE SELECT
c.5618G>A

Protein change:

R1824Q

Links:

dbSNP: rs397516322

NCBI 1000 Genomes Browser:

rs397516322

Molecular consequence:

NM_000260.4:c.5618G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127180.2:c.5504G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001369365.1:c.5471G>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000706352	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Uncertain significance (Feb 9, 2017)	germline	clinical testing	Citation Link,
SCV001412414	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jan 13, 2025)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 23208854, 27068579, 16679490, 28472130, 28492532
SCV001766145	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (Mar 25, 2025)	germline	clinical testing	Citation Link,
SCV001958143	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	Likely pathogenic	germline	clinical testing
SCV001971748	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	Likely pathogenic	germline	clinical testing

Help

Summary from all submissions

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

Citations

PubMed

A sensitive and specific diagnostic test for hearing loss using a microdroplet PCR-based approach and next generation sequencing.

Schrauwen I, Sommen M, Corneveaux JJ, Reiman RA, Hackett NJ, Claes C, Claes K, Bitner-Glindzicz M, Coucke P, Van Camp G, Huentelman MJ.

Am J Med Genet A. 2013 Jan;161A(1):145-52. doi: 10.1002/ajmg.a.35737. Epub 2012 Dec 3.

PubMed [citation]

PMID:: 23208854

DNA Diagnostics of Hereditary Hearing Loss: A Targeted Resequencing Approach Combined with a Mutation Classification System.

Sommen M, Schrauwen I, Vandeweyer G, Boeckx N, Corneveaux JJ, van den Ende J, Boudewyns A, De Leenheer E, Janssens S, Claes K, Verstreken M, Strenzke N, Predöhl F, Wuyts W, Mortier G, Bitner-Glindzicz M, Moser T, Coucke P, Huentelman MJ, Van Camp G.

Hum Mutat. 2016 Aug;37(8):812-9. doi: 10.1002/humu.22999. Epub 2016 May 6.

PubMed [citation]

PMID:: 27068579

See all PubMed Citations (5)

Details of each submission

From Eurofins Ntd Llc (ga), SCV000706352.3

#	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	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001412414.5

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

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1873 of the MYO7A protein (p.Arg1873Gln). 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 missense change has been observed in individual(s) with autosomal recessive nonsyndromic deafness (PMID: 23208854, 27068579; internal data). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as p.Arg1835Gln. ClinVar contains an entry for this variant (Variation ID: 43292). 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) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MYO7A protein function. This variant disrupts the p.Arg1873 amino acid residue in MYO7A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16679490, 28472130). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely 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, SCV001766145.2

#	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 supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27068579, 16963483, 31964843, 36147510, 27104957, 29196752, 23208854, 16679490, 27460420, 28944237, 28000701)

#	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, SCV001958143.1

#	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, SCV001971748.1

#	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: Jun 29, 2025

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