VCV000043337.6 - ClinVar

NM_000260.4(MYO7A):c.6577C>T (p.Leu2193Phe)

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.

(2)

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.

Uncertain significance

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000260.4(MYO7A):c.6577C>T (p.Leu2193Phe)

Variation ID: 43337 Accession: VCV000043337.6

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 11q13.5 11: 77214625 (GRCh38) [ NCBI UCSC ] 11: 76925670 (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	Feb 13, 2022	Mar 8, 2011

HGVS

Nucleotide	Protein	Molecular consequence
NM_000260.4:c.6577C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000251.3:p.Leu2193Phe	missense
NM_001127180.2:c.6457C>T	NP_001120652.1:p.Leu2153Phe	missense
NM_001369365.1:c.6430C>T	NP_001356294.1:p.Leu2144Phe	missense
NC_000011.10:g.77214625C>T
NC_000011.9:g.76925670C>T
NG_009086.2:g.91380C>T
LRG_1420:g.91380C>T
LRG_1420t1:c.6577C>T	LRG_1420p1:p.Leu2193Phe

... more HGVS ... less HGVS

Protein change

L2193F, L2144F, L2153F

Other names

Canonical SPDI

NC_000011.10:77214624:C:T

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.

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

Links

ClinGen: CA132443 dbSNP: rs397516333 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	4328	4339

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	Uncertain significance (1)	criteria provided, single submitter	Mar 8, 2011	RCV000036243.5
Usher syndrome type 1B	Uncertain significance (1)	no assertion criteria provided	Mar 21, 2020	RCV001826555.1

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 (Mar 08, 2011)	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: SCV000059895.6 First in ClinVar: May 03, 2013 Last updated: Jan 31, 2015	Comment: Variant classified as Uncertain Significance - Favor Pathogenic. The Leu2193Phe variant in MYO7A has not been reported in the literature nor previously identifi ed by … (more) Variant classified as Uncertain Significance - Favor Pathogenic. The Leu2193Phe variant in MYO7A has not been reported in the literature nor previously identifi ed by our laboratory. This residue is conserved across species and computational analyses (PolyPhen2, SIFT) suggest that the Leu2193Phe variant may impact the p rotein. However, this information is not predictive enough to assume pathogenici ty. It should be noted that this lab has only sequenced the MYO7A in 20 Asian pr obands and no Asian healthy controls. In addition, healthy control information i s unavailable from either public databases or scientific literature, such that t he full spectrum of benign variation has not yet been defined for this populatio n. Future analysis could reveal that the Leu2193Phe variant is common in this po pulation and therefore unlikely to be pathogenic. However, the presence of this variant in combination with another pathogenic variant in this gene, increases t he likelihood that this variant is pathogenic if found to be in trans (on separa te copies of the gene). In summary, the clinical significance of this variant ca nnot be determined with certainty at this time; however, we would lean towards a more likely pathogenic role. (less) Number of individuals with the variant: 1
Uncertain significance (Mar 21, 2020)	no assertion criteria provided Method: clinical testing	Usher syndrome type 1B Affected status: unknown Allele origin: germline	Natera, Inc. Accession: SCV002088550.1 First in ClinVar: Feb 13, 2022 Last updated: Feb 13, 2022

Comment:

Variant classified as Uncertain Significance - Favor Pathogenic. The Leu2193Phe variant in MYO7A has not been reported in the literature nor previously identifi ed by our laboratory. This residue is conserved across species and computational analyses (PolyPhen2, SIFT) suggest that the Leu2193Phe variant may impact the p rotein. However, this information is not predictive enough to assume pathogenici ty. It should be noted that this lab has only sequenced the MYO7A in 20 Asian pr obands and no Asian healthy controls. In addition, healthy control information i s unavailable from either public databases or scientific literature, such that t he full spectrum of benign variation has not yet been defined for this populatio n. Future analysis could reveal that the Leu2193Phe variant is common in this po pulation and therefore unlikely to be pathogenic. However, the presence of this variant in combination with another pathogenic variant in this gene, increases t he likelihood that this variant is pathogenic if found to be in trans (on separa te copies of the gene). In summary, the clinical significance of this variant ca nnot be determined with certainty at this time; however, we would lean towards a more likely pathogenic role.

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 rs397516333 ...

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 Aug 13, 2023

ClinVar Genomic variation as it relates to human health

NM_000260.4(MYO7A):c.6577C>T (p.Leu2193Phe)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs397516333 ...