NM_000260.4(MYO7A):c.5510T>C (p.Leu1837Pro) AND Usher syndrome type 1

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:: RCV003155267.1

Allele description [Variation Report for NM_000260.4(MYO7A):c.5510T>C (p.Leu1837Pro)]

NM_000260.4(MYO7A):c.5510T>C (p.Leu1837Pro)

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.5510T>C (p.Leu1837Pro)

HGVS:

NC_000011.10:g.77205491T>C
NG_009086.2:g.82246T>C
NM_000260.4:c.5510T>CMANE SELECT
NM_001127180.2:c.5396T>C
NM_001369365.1:c.5363T>C
NP_000251.3:p.Leu1837Pro
NP_001120652.1:p.Leu1799Pro
NP_001356294.1:p.Leu1788Pro
LRG_1420t1:c.5510T>C
LRG_1420:g.82246T>C
LRG_1420p1:p.Leu1837Pro
NC_000011.9:g.76916536T>C
NG_009086.1:g.82227T>C
NM_000260.3:c.5510T>C

Protein change:

L1788P

Links:

dbSNP: rs1385324903

NCBI 1000 Genomes Browser:

rs1385324903

Molecular consequence:

NM_000260.4:c.5510T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001127180.2:c.5396T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001369365.1:c.5363T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Usher syndrome type 1 (USH1)
Synonyms:: RETINITIS PIGMENTOSA AND CONGENITAL DEAFNESS; Usher syndrome, type I, French variety
Identifiers:: MONDO: MONDO:0010168; MedGen: C1568247; Orphanet: 231169; Orphanet: 886; OMIM: 276900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003844138	King Laboratory, University of Washington	criteria provided, single submitter (Li et al. (Genet Med. 2022))	Likely pathogenic (Feb 28, 2023)	unknown	research	PubMed (2) [See all records that cite these PMIDs] 36633841, 35802133

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003844138

King Laboratory, University of Washington

criteria provided, single submitter

(Li et al. (Genet Med. 2022))

Likely pathogenic
(Feb 28, 2023)

unknown

research

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	research

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, SCV003844138.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	PubMed (2)

Description

This variant occurred in compound heterozygosity with a likely pathogenic MYO7A missense variant in a patient with Usher syndrome including 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). This patient's family has no other history of hearing loss. This variant is a missense at a highly conserved site in a MyTH4 domain of the MYO7A protein and is predicted to be damaging by multiple in-silico tools. As of January 2023, this variant has been reported to ClinVar with conflicting interpretations and is found in 2 heterozygotes on gnomAD. Based on consistently predicted functional effect, compound heterozygosity with a known likely pathogenic variant, and goodness of fit of genotype to phenotype, we conclude that this variant is likely pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 25, 2025

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