VCV000043173.28 - ClinVar

NM_000260.4(MYO7A):c.2122A>G (p.Met708Val)

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.

(9)

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.

Conflicting classifications of pathogenicity
Uncertain significance(5); Likely benign(4)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000260.4(MYO7A):c.2122A>G (p.Met708Val)

Variation ID: 43173 Accession: VCV000043173.28

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 11q13.5 11: 77175399 (GRCh38) [ NCBI UCSC ] 11: 76886445 (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	Jan 31, 2015	Oct 20, 2024	Jan 21, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000260.4:c.2122A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000251.3:p.Met708Val	missense
NM_001127180.2:c.2122A>G	NP_001120652.1:p.Met708Val	missense
NM_001369365.1:c.2089A>G	NP_001356294.1:p.Met697Val	missense
NC_000011.10:g.77175399A>G
NC_000011.9:g.76886445A>G
NG_009086.2:g.52154A>G
LRG_1420:g.52154A>G
LRG_1420t1:c.2122A>G	LRG_1420p1:p.Met708Val

... more HGVS ... less HGVS

Protein change

M708V, M697V

Other names

Canonical SPDI

NC_000011.10:77175398: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.

0.00040 (G)

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

The Genome Aggregation Database (gnomAD) 0.00001

Trans-Omics for Precision Medicine (TOPMed) 0.00003

The Genome Aggregation Database (gnomAD), exomes 0.00024

Exome Aggregation Consortium (ExAC) 0.00026

1000 Genomes Project 30x 0.00031

1000 Genomes Project 0.00040

Links

ClinGen: CA132235 dbSNP: rs397516293 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	4333	4344

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	Likely benign (1)	criteria provided, single submitter	Aug 5, 2010	RCV000036077.5
Autosomal recessive nonsyndromic hearing loss 2 Usher syndrome type 1	Uncertain significance (1)	criteria provided, single submitter	Jan 20, 2017	RCV000665188.1
Usher syndrome type 1	Uncertain significance (1)	criteria provided, single submitter	May 18, 2021	RCV001526753.2
not provided	Conflicting interpretations of pathogenicity (4)	criteria provided, conflicting classifications	Jan 21, 2024	RCV001288311.24
Autosomal dominant nonsyndromic hearing loss 11	Likely benign (1)	criteria provided, single submitter	Jul 14, 2021	RCV001578680.2
Autosomal recessive nonsyndromic hearing loss 2	Uncertain significance (1)	criteria provided, single submitter	Jul 14, 2021	RCV001578681.2

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.
Uncertain significance (Dec 05, 2019)	criteria provided, single submitter (Athena Diagnostics Criteria) Method: clinical testing	not provided Affected status: unknown Allele origin: unknown	Athena Diagnostics Accession: SCV001475320.1 First in ClinVar: Jan 26, 2021 Last updated: Jan 26, 2021
Likely benign (Aug 01, 2023)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV004131116.10 First in ClinVar: Nov 20, 2023 Last updated: Oct 20, 2024	Comment: MYO7A: BP4 Number of individuals with the variant: 1
Uncertain significance (Jan 20, 2017)	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018)) Method: clinical testing	Usher syndrome type 1 Autosomal recessive nonsyndromic hearing loss 2 Affected status: unknown Allele origin: unknown	Counsyl Accession: SCV000789262.1 First in ClinVar: Aug 05, 2018 Last updated: Aug 05, 2018
Likely benign (Aug 05, 2010)	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: SCV000059729.6 First in ClinVar: May 03, 2013 Last updated: Jan 31, 2015	Comment: Met708Val in exon 18 of MYO7A: This variant is not expected to have clinical sig nificance because this residue is not highly conserved across species. … (more) Met708Val in exon 18 of MYO7A: This variant is not expected to have clinical sig nificance because this residue is not highly conserved across species. In additi on, computational analyses (PolyPhen, SIFT, AlignGVGD) do not suggest a high lik elihood of clinical significance. (less) Number of individuals with the variant: 1
Uncertain significance (May 18, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Usher syndrome type 1 Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV001737268.1 First in ClinVar: Jun 19, 2021 Last updated: Jun 19, 2021	Sex: mixed
Uncertain significance (Jul 14, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Autosomal recessive nonsyndromic hearing loss 2 Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV001805952.1 First in ClinVar: Aug 25, 2021 Last updated: Aug 25, 2021	Sex: mixed
Likely benign (Jul 14, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Autosomal dominant nonsyndromic hearing loss 11 Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV001805951.1 First in ClinVar: Aug 25, 2021 Last updated: Aug 25, 2021	Sex: mixed
Uncertain significance (Feb 27, 2019)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Revvity Omics, Revvity Accession: SCV003817859.2 First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024
Likely benign (Jan 21, 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: SCV001650621.4 First in ClinVar: May 23, 2021 Last updated: Feb 20, 2024

Comment:

Met708Val in exon 18 of MYO7A: This variant is not expected to have clinical sig nificance because this residue is not highly conserved across species. In additi on, computational analyses (PolyPhen, SIFT, AlignGVGD) do not suggest a high lik elihood of clinical significance.

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:

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs397516293 ...

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 Oct 20, 2024

ClinVar Genomic variation as it relates to human health

NM_000260.4(MYO7A):c.2122A>G (p.Met708Val)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs397516293 ...