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NM_000260.4(MYO7A):c.5552T>C (p.Leu1851Pro) AND Autosomal recessive nonsyndromic hearing loss 2

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Feb 28, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV003155566.1

Allele description [Variation Report for NM_000260.4(MYO7A):c.5552T>C (p.Leu1851Pro)]

NM_000260.4(MYO7A):c.5552T>C (p.Leu1851Pro)

Gene:
MYO7A:myosin VIIA [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11q13.5
Genomic location:
Preferred name:
NM_000260.4(MYO7A):c.5552T>C (p.Leu1851Pro)
HGVS:
  • NC_000011.10:g.77205533T>C
  • NG_009086.2:g.82288T>C
  • NM_000260.4:c.5552T>CMANE SELECT
  • NM_001127180.2:c.5438T>C
  • NM_001369365.1:c.5405T>C
  • NP_000251.3:p.Leu1851Pro
  • NP_001120652.1:p.Leu1813Pro
  • NP_001356294.1:p.Leu1802Pro
  • LRG_1420t1:c.5552T>C
  • LRG_1420:g.82288T>C
  • LRG_1420p1:p.Leu1851Pro
  • NC_000011.9:g.76916578T>C
Protein change:
L1802P
Molecular consequence:
  • NM_000260.4:c.5552T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127180.2:c.5438T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369365.1:c.5405T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Autosomal recessive nonsyndromic hearing loss 2
Synonyms:
NEUROSENSORY NONSYNDROMIC RECESSIVE DEAFNESS 2; Deafness, autosomal recessive 2
Identifiers:
MONDO: MONDO:0010807; MedGen: C1838701; Orphanet: 90636; OMIM: 600060

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003844139King Laboratory, University of Washington
criteria provided, single submitter

(Li et al. (Genet Med. 2022))		Likely pathogenic
(Feb 28, 2023) 		unknownresearch

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownyesnot providednot providednot providednot providednot providedresearch

Citations

PubMed

Association of Genetic Diagnoses for Childhood-Onset Hearing Loss With Cochlear Implant Outcomes.

Carlson RJ, Walsh T, Mandell JB, Aburayyan A, Lee MK, Gulsuner S, Horn DL, Ou HC, Sie KCY, Mancl L, Rubinstein J, King MC.

JAMA Otolaryngol Head Neck Surg. 2023 Mar 1;149(3):212-222. doi: 10.1001/jamaoto.2022.4463.

PubMed [citation]
PMID:
36633841
PMCID:
PMC9857764

Clinical evaluation and etiologic diagnosis of hearing loss: A clinical practice resource of the American College of Medical Genetics and Genomics (ACMG).

Li MM, Tayoun AA, DiStefano M, Pandya A, Rehm HL, Robin NH, Schaefer AM, Yoshinaga-Itano C; ACMG Professional Practice and Guidelines Committee. Electronic address: documents@acmg.net..

Genet Med. 2022 Jul;24(7):1392-1406. doi: 10.1016/j.gim.2022.03.018. Epub 2022 May 10.

PubMed [citation]
PMID:
35802133

Details of each submission

From King Laboratory, University of Washington, SCV003844139.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedresearch PubMed (2)

Description

This variant occurred in compound heterozygosity with a known, likely pathogenic MYO7A missense variant in two siblings with bilateral sensorineural hearing loss of onset <18 years, in a study of pediatric hearing loss conducted by the King Laboratory (Carlson RJ et al. JAMA-OtoHNS 2023). At the time of recruitment, the siblings did not have any known visual impairment (age 21y and 12y). This patient's family has no other history of hearing loss. This variant is a missense at a highly conserved site in the MyTH4 domain of the MYO7A protein and is predicted to be damaging by multiple in-silico tools. As of January 2023, this variant has not been reported to ClinVar and is not found on gnomAD. Based on consistently predicted functional effect, co-segregation with the phenotype in the family, compound heterozygosity with a known likely pathogenic variant, and goodness of fit of genotype to phenotype, we conclude that this variant is likely pathogenic.

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

Last Updated: Apr 1, 2023