NM_000260.4(MYO7A):c.4544_4551delinsCA (p.Glu1515_Met1517delinsAla) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (4 submissions)
Last evaluated:: Oct 13, 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:: RCV000725794.8

Allele description [Variation Report for NM_000260.4(MYO7A):c.4544_4551delinsCA (p.Glu1515_Met1517delinsAla)]

NM_000260.4(MYO7A):c.4544_4551delinsCA (p.Glu1515_Met1517delinsAla)

Gene:

MYO7A:myosin VIIA [Gene - OMIM - HGNC]

Variant type:

Indel

Cytogenetic location:

11q13.5

Genomic location:

Preferred name:

NM_000260.4(MYO7A):c.4544_4551delinsCA (p.Glu1515_Met1517delinsAla)

HGVS:

NC_000011.10:g.77198597_77198604delinsCA
NG_009086.2:g.75352_75359delinsCA
NM_000260.4:c.4544_4551delinsCAMANE SELECT
NM_001127180.2:c.4544_4551delinsCA
NM_001369365.1:c.4511_4518delinsCA
NP_000251.3:p.Glu1515_Met1517delinsAla
NP_001120652.1:p.Glu1515_Met1517delinsAla
NP_001356294.1:p.Glu1504_Met1506delinsAla
LRG_1420t1:c.4544_4551delinsCA
LRG_1420:g.75352_75359delinsCA
LRG_1420p1:p.Glu1515_Met1517delinsAla
NC_000011.9:g.76909642_76909649delinsCA
NG_009086.1:g.75333_75340delinsCA
NM_000260.4:c.4544_4551delinsCA
c.4544_4551delinsCA

Links:

dbSNP: rs111033259

NCBI 1000 Genomes Browser:

rs111033259

Observations:

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
SCV000339454	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Likely pathogenic (Feb 1, 2016)	germline	clinical testing	Citation Link,
SCV001412828	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 8, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16963483, 27743452, 28492532
SCV004168034	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (Oct 13, 2023)	germline	clinical testing	Citation Link,
SCV005197530	Clinical Genetics Laboratory, Skane University Hospital Lund	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Sep 25, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Development of a genotyping microarray for Usher syndrome.

Cremers FP, Kimberling WJ, Külm M, de Brouwer AP, van Wijk E, te Brinke H, Cremers CW, Hoefsloot LH, Banfi S, Simonelli F, Fleischhauer JC, Berger W, Kelley PM, Haralambous E, Bitner-Glindzicz M, Webster AR, Saihan Z, De Baere E, Leroy BP, Silvestri G, McKay GJ, Koenekoop RK, et al.

J Med Genet. 2007 Feb;44(2):153-60. Epub 2006 Sep 8.

PubMed [citation]

PMID:: 16963483
PMCID:: PMC2598068

The combination of vestibular impairment and congenital sensorineural hearing loss predisposes patients to ocular anomalies, including Usher syndrome.

Kletke S, Batmanabane V, Dai T, Vincent A, Li S, Gordon KA, Papsin BC, Cushing SL, Héon E.

Clin Genet. 2017 Jul;92(1):26-33. doi: 10.1111/cge.12895. Epub 2017 Jan 16.

PubMed [citation]

PMID:: 27743452

See all PubMed Citations (4)

Details of each submission

From Eurofins Ntd Llc (ga), SCV000339454.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	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		1	not provided	not provided	not provided

From Invitae, SCV001412828.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This variant, c.4544_4551delinsCA, is a complex sequence change that results in the deletion of 3 and insertion of 1 amino acid(s) in the MYO7A protein (p.Glu1515_Met1517delinsAla). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This variant has been observed in individual(s) with clinical features of Usher syndrome (PMID: 16963483, 27743452; Invitae). 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 c.4543_4551delGAGATCATGinsGCA. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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

From GeneDx, SCV004168034.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

In-frame deletion of 3 amino acids and an insertion of 1 amino acid in a non-repeat region; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 16963483, 33576163, 27743452)

#	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 Laboratory, Skane University Hospital Lund, SCV005197530.1

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

#	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: Aug 25, 2024

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