NM_000260.4(MYO7A):c.2023C>T (p.Arg675Cys) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 13, 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:: RCV003323677.2

Allele description [Variation Report for NM_000260.4(MYO7A):c.2023C>T (p.Arg675Cys)]

NM_000260.4(MYO7A):c.2023C>T (p.Arg675Cys)

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.2023C>T (p.Arg675Cys)

HGVS:

NC_000011.10:g.77174843C>T
NG_009086.2:g.51598C>T
NM_000260.4:c.2023C>TMANE SELECT
NM_001127180.2:c.2023C>T
NM_001369365.1:c.1990C>T
NP_000251.3:p.Arg675Cys
NP_001120652.1:p.Arg675Cys
NP_001356294.1:p.Arg664Cys
LRG_1420t1:c.2023C>T
LRG_1420:g.51598C>T
LRG_1420p1:p.Arg675Cys
NC_000011.9:g.76885889C>T
NG_009086.1:g.51580C>T
NM_000260.3:c.2023C>T

Protein change:

R664C

Links:

dbSNP: rs782459520

NCBI 1000 Genomes Browser:

rs782459520

Molecular consequence:

NM_000260.4:c.2023C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001127180.2:c.2023C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001369365.1:c.1990C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004030131	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Jul 13, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 23967202, 34426522, 35453549 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004030131

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Jul 13, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Targeted exon sequencing successfully discovers rare causative genes and clarifies the molecular epidemiology of Japanese deafness patients.

Miyagawa M, Naito T, Nishio SY, Kamatani N, Usami S.

PLoS One. 2013;8(8):e71381. doi: 10.1371/journal.pone.0071381.

PubMed [citation]

PMID:: 23967202
PMCID:: PMC3742761

The genetic structure of the Turkish population reveals high levels of variation and admixture.

Kars ME, Başak AN, Onat OE, Bilguvar K, Choi J, Itan Y, Çağlar C, Palvadeau R, Casanova JL, Cooper DN, Stenson PD, Yavuz A, Buluş H, Günel M, Friedman JM, Özçelik T.

Proc Natl Acad Sci U S A. 2021 Sep 7;118(36). doi:pii: e2026076118. 10.1073/pnas.2026076118. Erratum in: Proc Natl Acad Sci U S A. 2021 Dec 28;118(52):e2120031118. doi: 10.1073/pnas.2120031118.

PubMed [citation]

PMID:: 34426522
PMCID:: PMC8433500

See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004030131.1

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

Description

Variant summary: MYO7A c.2023C>T (p.Arg675Cys) results in a non-conservative amino acid change located in the myosin head, motor domain (IPR001609) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 247790 control chromosomes. c.2023C>T has been reported in the literature in at least two heterozygous individuals affected with hearing loss (Joo_2022). The variant has also been reported in additional individuals with clinical features of MYO7A-related disorders without strong evidence for causality (e.g., Miyagawa_2013, Kars_2021) These data indicate that the variant may be associated with disease. 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: 35453549, 34426522, 23967202). Four submitters have cited clinical-significance assessments for this variant to ClinVar after 2014, and all submitters classified the variant as a variant of uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly 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

Last Updated: Aug 25, 2024

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