NM_016239.4(MYO15A):c.6442T>A (p.Trp2148Arg) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 8, 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:: RCV003560839.2

Allele description [Variation Report for NM_016239.4(MYO15A):c.6442T>A (p.Trp2148Arg)]

NM_016239.4(MYO15A):c.6442T>A (p.Trp2148Arg)

Gene:

MYO15A:myosin XVA [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17p11.2

Genomic location:

Preferred name:

NM_016239.4(MYO15A):c.6442T>A (p.Trp2148Arg)

HGVS:

NC_000017.11:g.18146040T>A
NG_011634.2:g.42335T>A
NM_016239.4:c.6442T>AMANE SELECT
NP_057323.3:p.Trp2148Arg
NC_000017.10:g.18049354T>A

Protein change:

W2148R

Links:

dbSNP: rs2142355107

NCBI 1000 Genomes Browser:

rs2142355107

Molecular consequence:

NM_016239.4:c.6442T>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004298157	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 8, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 27635202, 33208113, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004298157

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 8, 2023)

germline

clinical testing

PubMed (3)
[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	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Screening of DFNB3 in Iranian families with autosomal recessive non-syndromic hearing loss reveals a novel pathogenic mutation in the MyTh4 domain of the MYO15A gene in a linked family.

Reiisi S, Tabatabaiefar MA, Sanati MH, Chaleshtori MH.

Iran J Basic Med Sci. 2016 Jul;19(7):772-8.

PubMed [citation]

PMID:: 27635202
PMCID:: PMC5010850

Novel MYO15A variants are associated with hearing loss in the two Iranian pedigrees.

Khatami S, Askari M, Bahreini F, Hashemzadeh-Chaleshtori M, Hematian S, Asgharzade S.

BMC Med Genet. 2020 Nov 18;21(1):226. doi: 10.1186/s12881-020-01168-x.

PubMed [citation]

PMID:: 33208113
PMCID:: PMC7672957

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004298157.1

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

Description

For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MYO15A protein function. ClinVar contains an entry for this variant (Variation ID: 1301944). This missense change has been observed in individual(s) with nonsyndromic deafness (PMID: 27635202, 33208113). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 2148 of the MYO15A protein (p.Trp2148Arg).

#	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: Sep 29, 2024

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