VCV000043274.32 - ClinVar

NM_000260.4(MYO7A):c.5156A>G (p.Tyr1719Cys)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(13)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Benign/Likely benign

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000260.4(MYO7A):c.5156A>G (p.Tyr1719Cys)

Variation ID: 43274 Accession: VCV000043274.32

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 11q13.5 11: 77202412 (GRCh38) [ NCBI UCSC ] 11: 76913457 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Oct 9, 2016	Sep 29, 2024	Jan 31, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000260.4:c.5156A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000251.3:p.Tyr1719Cys	missense
NM_001127180.2:c.5042A>G	NP_001120652.1:p.Tyr1681Cys	missense
NM_001369365.1:c.5009A>G	NP_001356294.1:p.Tyr1670Cys	missense
NC_000011.10:g.77202412A>G
NC_000011.9:g.76913457A>G
NG_009086.2:g.79167A>G
LRG_1420:g.79167A>G
LRG_1420t1:c.5156A>G	LRG_1420p1:p.Tyr1719Cys
	Q13402:p.Tyr1719Cys

... more HGVS ... less HGVS

Protein change

Y1719C, Y1681C, Y1670C

Other names

p.Y1719C:TAT>TGT
NM_000260.3(MYO7A):c.5156A>G(p.Tyr1719Cys)
NM_001127180.1(MYO7A):c.5042A>G(p.Tyr1681Cys)

Canonical SPDI

NC_000011.10:77202411:A:G

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.04393 (G)

Allele frequency Help The frequency of the allele represented by this VCV record.

Trans-Omics for Precision Medicine (TOPMed) 0.04990

The Genome Aggregation Database (gnomAD), exomes 0.01609

Exome Aggregation Consortium (ExAC) 0.02398

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.04240

1000 Genomes Project 0.04393

1000 Genomes Project 30x 0.04622

The Genome Aggregation Database (gnomAD) 0.04825

Links

ClinGen: CA132375 UniProtKB: Q13402#VAR_009344 dbSNP: rs77625410 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
MYO7A		-	-	GRCh38 GRCh37	4340	4351

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
not specified	Benign (3)	criteria provided, multiple submitters, no conflicts	Feb 6, 2015	RCV000036179.21
Autosomal dominant nonsyndromic hearing loss 11	Likely benign (1)	criteria provided, single submitter	Apr 27, 2017	RCV000271936.13
Autosomal recessive nonsyndromic hearing loss 2	Likely benign (1)	criteria provided, single submitter	Apr 27, 2017	RCV000367756.13
Usher syndrome type 1	Benign/Likely benign (2)	criteria provided, multiple submitters, no conflicts	May 31, 2018	RCV000677322.13
not provided	Benign/Likely benign (4)	criteria provided, multiple submitters, no conflicts	Jan 31, 2024	RCV000755320.26
Usher syndrome type 1B	Benign (1)	no assertion criteria provided	Sep 16, 2020	RCV001273508.9
Autosomal dominant nonsyndromic hearing loss 11 Autosomal recessive nonsyndromic hearing loss 2 Usher syndrome type 1	Benign (1)	criteria provided, single submitter	Apr 28, 2022	RCV002496553.8

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Benign (Dec 28, 2018)	criteria provided, single submitter (Athena Diagnostics Criteria) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Athena Diagnostics Accession: SCV001144668.1 First in ClinVar: Jan 19, 2020 Last updated: Jan 19, 2020
Benign (Apr 28, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Usher syndrome type 1 Autosomal recessive nonsyndromic hearing loss 2 Autosomal dominant nonsyndromic hearing loss 11 Affected status: unknown Allele origin: unknown	Fulgent Genetics, Fulgent Genetics Accession: SCV002804671.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022
Benign (Apr 05, 2013)	criteria provided, single submitter (GeneDx Variant Classification (06012015)) Method: clinical testing	not specified Affected status: yes Allele origin: germline	GeneDx Accession: SCV000170594.9 First in ClinVar: Jun 23, 2014 Last updated: Oct 09, 2016	Comment: This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more) This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
Benign (May 31, 2018)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: curation	Usher syndrome type 1 Affected status: unknown Allele origin: unknown	SIB Swiss Institute of Bioinformatics Accession: SCV000803532.1 First in ClinVar: Aug 20, 2018 Last updated: Aug 20, 2018	Comment: This variant is interpreted as a Benign, for Usher syndrome 1B, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: BS1 => Allele frequency … (more) This variant is interpreted as a Benign, for Usher syndrome 1B, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: BS1 => Allele frequency is greater than expected for disorder. BS2 => Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age. 6 homozygotes in ExAC. (less)
Benign (Feb 06, 2015)	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000229851.5 First in ClinVar: Jun 28, 2015 Last updated: Oct 09, 2016	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=MYO7A Number of individuals with the variant: 1 Sex: mixed
Benign (Jun 23, 2009)	criteria provided, single submitter (LMM Criteria) Method: clinical testing	not specified Affected status: not provided Allele origin: germline	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000059831.6 First in ClinVar: May 03, 2013 Last updated: Feb 17, 2019	Publications: PubMed (6) PubMed: 10094549‚ 10425080‚ 12112664‚ 16963483‚ 17960123‚ 16679490 Number of individuals with the variant: 104
Likely benign (Apr 27, 2017)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Usher syndrome type 1 Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000374424.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more) This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
Likely benign (Apr 27, 2017)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Autosomal recessive nonsyndromic hearing loss 2 Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000374425.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more) This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
Likely benign (Apr 27, 2017)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Autosomal dominant nonsyndromic hearing loss 11 Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000374423.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Publications: PubMed (2) PubMed: 10094549‚ 17960123 Comment: This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more) This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
Benign (Jan 31, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001727962.4 First in ClinVar: Jun 15, 2021 Last updated: Feb 20, 2024
Benign (Nov 06, 2023)	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV000604426.7 First in ClinVar: Oct 09, 2016 Last updated: Feb 20, 2024
Likely benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: not provided	not provided (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005211580.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024
Benign (Sep 16, 2020)	no assertion criteria provided Method: clinical testing	Usher syndrome type 1B Affected status: unknown Allele origin: germline	Natera, Inc. Accession: SCV001456619.1 First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021
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Comment:

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Comment:

This variant is interpreted as a Benign, for Usher syndrome 1B, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: BS1 => Allele frequency is greater than expected for disorder. BS2 => Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age. 6 homozygotes in ExAC.

Comment:

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.

Comment:

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Analysis of MYO7A in a Moroccan family with Usher syndrome type 1B: novel loss-of-function mutation and non-pathogenicity of p.Y1719C.	Boulouiz R	Molecular vision	2007	PMID: 17960123
Development of a genotyping microarray for Usher syndrome.	Cremers FP	Journal of medical genetics	2007	PMID: 16963483
Survey of the frequency of USH1 gene mutations in a cohort of Usher patients shows the importance of cadherin 23 and protocadherin 15 genes and establishes a detection rate of above 90%.	Roux AF	Journal of medical genetics	2006	PMID: 16679490
Mutations in myosin VIIA (MYO7A) and usherin (USH2A) in Spanish patients with Usher syndrome types I and II, respectively.	Nájera C	Human mutation	2002	PMID: 12112664
Identification of three novel mutations in the MYO7A gene.	Cuevas JM	Human mutation	1999	PMID: 10425080
Twelve novel myosin VIIA mutations in 34 patients with Usher syndrome type I: confirmation of genetic heterogeneity.	Janecke AR	Human mutation	1999	PMID: 10094549
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=MYO7A	-	-	-	-

Text-mined citations for rs77625410 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 25, 2024

ClinVar Genomic variation as it relates to human health

NM_000260.4(MYO7A):c.5156A>G (p.Tyr1719Cys)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs77625410 ...