NM_000260.3(MYO7A):c.4544_4551delAGATCATGinsCA (p.Glu1515_Met1517delinsAla) AND Usher syndrome, type 1

Clinical significance:Conflicting interpretations of pathogenicity, Likely pathogenic(1);Pathogenic(1) (Last evaluated: Feb 1, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000036150.3

Allele description

NM_000260.3(MYO7A):c.4544_4551delAGATCATGinsCA (p.Glu1515_Met1517delinsAla)

Gene:
MYO7A:myosin VIIA [Gene - OMIM - HGNC]
Variant type:
Indel
Cytogenetic location:
11q13.5
Genomic location:
Preferred name:
NM_000260.3(MYO7A):c.4544_4551delAGATCATGinsCA (p.Glu1515_Met1517delinsAla)
HGVS:
  • NC_000011.10:g.77198597_77198604delAGATCATGinsCA
  • NG_009086.1:g.75333_75340delAGATCATGinsCA
  • NM_000260.3:c.4544_4551delAGATCATGinsCA
  • NP_000251.3:p.Glu1515_Met1517delinsAla
  • NC_000011.9:g.76909642_76909649delAGATCATGinsCA
  • NC_000011.9:g.76909642_76909649delinsCA
  • NM_000260.3:c.4544_4551delinsCA
  • c.4544_4551delinsCA
Links:
dbSNP: rs111033259
NCBI 1000 Genomes Browser:
rs111033259
Molecular consequence:
  • NM_000260.3:c.4544_4551delAGATCATGinsCA - inframe_variant - [Sequence Ontology: SO:0001650]
Observations:
2

Condition(s)

Name:
Usher syndrome, type 1 (USH1)
Synonyms:
Usher syndrome, type 1B
Identifiers:
MedGen: C1568247; Orphanet: 231169; Orphanet: 886; OMIM: 276900
Age of onset:
Infancy
Prevalence:
1-9 / 100 000 231169886

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000059802Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicinecriteria provided, single submitter
Pathogenic
(Jul 7, 2011)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV000339454Emory Genetics Laboratory,Emory Universitycriteria provided, single submitter
Likely pathogenic
(Feb 1, 2016)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot providednot providednot providedclinical testing
not providedgermlinenot provided42not providednot providednot providedclinical 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

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]
PMID:
24033266
PMCID:
PMC3995020

Details of each submission

From Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine, SCV000059802.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided4not providednot providedclinical testing PubMed (2)

Description

The Glu1515_Met1517delinsAla variant in MYO7A has been identified in three probands with Usher syndrome (personal communication, W. Kimberling and two in our laboratory). The variant replaces three amino acids with a single new amino acid and is therefore likely to impact protein function. In addition, two probands have a second pathogenic variant in MYO7A which further supports a causative role. And finally, one proband’s affected sibling was also found to harbor both the 6439-2A>G variant and this MYO7A variant and parental testing showed the variants were in trans (on two separate copies of the gene). In summary, this data supports the classification of this variant as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided4not provided2not provided

From Emory Genetics Laboratory,Emory University, SCV000339454.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided1not providednot providednot provided

Last Updated: Mar 7, 2017