NM_000260.4(MYO7A):c.640G>A (p.Gly214Arg) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Nov 27, 2023
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:: RCV000724325.20

Allele description [Variation Report for NM_000260.4(MYO7A):c.640G>A (p.Gly214Arg)]

NM_000260.4(MYO7A):c.640G>A (p.Gly214Arg)

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.640G>A (p.Gly214Arg)

HGVS:

NC_000011.10:g.77156909G>A
NG_009086.2:g.33664G>A
NM_000260.4:c.640G>AMANE SELECT
NM_001127180.2:c.640G>A
NM_001369365.1:c.607G>A
NP_000251.3:p.Gly214Arg
NP_001120652.1:p.Gly214Arg
NP_001356294.1:p.Gly203Arg
LRG_1420t1:c.640G>A
LRG_1420:g.33664G>A
LRG_1420p1:p.Gly214Arg
NC_000011.9:g.76867955G>A
NG_009086.1:g.33646G>A
NM_000260.3:c.640G>A
Q13402:p.Gly214Arg
c.640G>A

Protein change:

G203R

Links:

UniProtKB: Q13402#VAR_009320; dbSNP: rs111033283

NCBI 1000 Genomes Browser:

rs111033283

Molecular consequence:

NM_000260.4:c.640G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127180.2:c.640G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001369365.1:c.607G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000232036	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Pathogenic (Oct 21, 2014)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 16470552, 18181211, 19683999, 20497194, 9382091 Citation Link,
SCV000962274	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 27, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 9382091, 16470552, 20497194, 24199935, 26969326, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000232036

Eurofins Ntd Llc (ga)

criteria provided, single submitter

(EGL Classification Definitions 2015)

Pathogenic
(Oct 21, 2014)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link,

SCV000962274

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 27, 2023)

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	unknown	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutation spectrum of MYO7A and evaluation of a novel nonsyndromic deafness DFNB2 allele with residual function.

Riazuddin S, Nazli S, Ahmed ZM, Yang Y, Zulfiqar F, Shaikh RS, Zafar AU, Khan SN, Sabar F, Javid FT, Wilcox ER, Tsilou E, Boger ET, Sellers JR, Belyantseva IA, Riazuddin S, Friedman TB.

Hum Mutat. 2008 Apr;29(4):502-11. doi: 10.1002/humu.20677.

PubMed [citation]

PMID:: 18181211

Microarray-based mutation analysis of 183 Spanish families with Usher syndrome.

Jaijo T, Aller E, García-García G, Aparisi MJ, Bernal S, Avila-Fernández A, Barragán I, Baiget M, Ayuso C, Antiñolo G, Díaz-Llopis M, Külm M, Beneyto M, Nájera C, Millán JM.

Invest Ophthalmol Vis Sci. 2010 Mar;51(3):1311-7. doi: 10.1167/iovs.09-4085. Epub 2009 Aug 13.

PubMed [citation]

PMID:: 19683999

See all PubMed Citations (8)

Details of each submission

From Eurofins Ntd Llc (ga), SCV000232036.5

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

#	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, SCV000962274.6

#	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 replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 214 of the MYO7A protein (p.Gly214Arg). This variant is present in population databases (rs111033283, gnomAD 0.006%). This missense change has been observed in individual(s) with Usher syndrome (PMID: 9382091, 16470552, 20497194, 24199935, 26969326). 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: 43327). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MYO7A protein function with a positive predictive value of 95%. 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: Oct 13, 2024

ClinVar

Relating variation to medicine