NM_015404.4(WHRN):c.1381A>C (p.Met461Leu) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 15, 2017
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:: RCV000611623.4

Allele description [Variation Report for NM_015404.4(WHRN):c.1381A>C (p.Met461Leu)]

NM_015404.4(WHRN):c.1381A>C (p.Met461Leu)

Gene:

WHRN:whirlin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9q32

Genomic location:

Preferred name:

NM_015404.4(WHRN):c.1381A>C (p.Met461Leu)

HGVS:

NC_000009.12:g.114424369T>G
NG_016700.1:g.86088A>C
NM_001083885.3:c.232A>C
NM_001173425.2:c.1381A>C
NM_001346890.1:c.328A>C
NM_015404.4:c.1381A>CMANE SELECT
NP_001077354.2:p.Met78Leu
NP_001166896.1:p.Met461Leu
NP_001333819.1:p.Met110Leu
NP_056219.3:p.Met461Leu
LRG_1094t1:c.1381A>C
LRG_1094:g.86088A>C
LRG_1094p1:p.Met461Leu
NC_000009.11:g.117186649T>G
NM_015404.2:c.1381A>C
NM_015404.3:c.1381A>C

Protein change:

M110L

Links:

dbSNP: rs144878400

NCBI 1000 Genomes Browser:

rs144878400

Molecular consequence:

NM_001083885.3:c.232A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001173425.2:c.1381A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001346890.1:c.328A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_015404.4:c.1381A>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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
SCV000711012	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Uncertain significance (Aug 15, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000711012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Uncertain significance
(Aug 15, 2017)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	2	2	not provided	not provided	not provided	clinical 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

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000711012.2

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

Description

The p.Met461Leu variant in WHRN has not been previously reported in individuals with hearing loss, but has been identified in 74/126578 of European chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org/; d bSNP rs144878400). However, this frequency is not high enough to rule out pathog enicity. Computational prediction tools and conservation analysis suggest that t his variant may not impact the protein, though this information is not predictiv e enough to rule out pathogenicity. In summary, the clinical significance of the p.Met461Leu variant is uncertain. ACMG/AMP Criteria applied: BP4.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		2	not provided	2	not provided

Last Updated: Sep 29, 2024

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