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NM_000260.4(MYO7A):c.1401_1403dup (p.Arg467_His468insGln) AND not specified

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Apr 17, 2024
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:
RCV000036049.7

Allele description [Variation Report for NM_000260.4(MYO7A):c.1401_1403dup (p.Arg467_His468insGln)]

NM_000260.4(MYO7A):c.1401_1403dup (p.Arg467_His468insGln)

Gene:
MYO7A:myosin VIIA [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
11q13.5
Genomic location:
Preferred name:
NM_000260.4(MYO7A):c.1401_1403dup (p.Arg467_His468insGln)
HGVS:
  • NC_000011.10:g.77162177_77162179dup
  • NG_009086.2:g.38932_38934dup
  • NM_000260.4:c.1401_1403dupMANE SELECT
  • NM_001127180.2:c.1401_1403dup
  • NM_001369365.1:c.1368_1370dup
  • NP_000251.3:p.Arg467_His468insGln
  • NP_001120652.1:p.Arg467_His468insGln
  • NP_001356294.1:p.Arg456_His457insGln
  • LRG_1420t1:c.1401_1403dup
  • LRG_1420:g.38932_38934dup
  • LRG_1420p1:p.Arg467_His468insGln
  • NC_000011.9:g.76873222_76873223insGCA
  • NC_000011.9:g.76873223_76873225dup
  • NM_000260.3:c.1403_1404insGCA
  • NM_000260.3:c.1403_1404insGCA
  • NM_000260.4:c.1401_1403dupGCAMANE SELECT
  • c.1403_1404insGCA
Links:
dbSNP: rs111033219
NCBI 1000 Genomes Browser:
rs111033219
Molecular consequence:
  • NM_000260.4:c.1401_1403dup - inframe_insertion - [Sequence Ontology: SO:0001821]
  • NM_001127180.2:c.1401_1403dup - inframe_insertion - [Sequence Ontology: SO:0001821]
  • NM_001369365.1:c.1368_1370dup - inframe_insertion - [Sequence Ontology: SO:0001821]
Observations:
1

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000059701Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)
Uncertain significance
(Apr 5, 2018)
germlineclinical testing

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

SCV005077617Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)
Uncertain significance
(Apr 17, 2024)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlinenot provided21not providednot providednot providedclinical testing

Citations

PubMed

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

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
See all PubMed Citations (5)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000059701.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testing PubMed (2)

Description

The p.Arg467_His468insGln variant in MYO7A has been reported in the heterozygous state in 2 individuals with Usher syndrome type 1 (Weston 1996). This variant w as absent from large population studies, though the ability of these studies to accurately detect indels may be limited. This variant is an insertion of 1 amino acid at position 467 and is not predicted to alter the protein reading-frame. I t is unclear if this insertion will impact the protein. In summary, the clinical significance of the p.Arg467_His468insGln variant is uncertain. ACMG/AMP Criter ia applied: PM2; PM4_Supporting.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided2not provided1not provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV005077617.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

Variant summary: MYO7A c.1401_1403dupGCA (p.Arg467_His468insGln) results in an in-frame insertion that is predicted to insert one amino acid into the Myosin head, motor domain (IPR001609) of the encoded protein. The variant was absent in 230428 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1401_1403dupGCA has been reported in the literature as a non-informative heterozygous genotype (without a second allele specified) in an affected proband with Usher syndrome as well as in her unaffected mother and unaffected maternal grandmother (Weston_1996). These report(s) do not provide unequivocal conclusions about association of the variant with Usher Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 16963483, 20146813, 9718356, 8900236). ClinVar contains an entry for this variant (Variation ID: 43145). Based on the evidence outlined above, the variant was classified as uncertain significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024