NM_004700.4(KCNQ4):c.803CCT[1] (p.Ser269del) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 26, 2018
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:: RCV000825943.12

Allele description [Variation Report for NM_004700.4(KCNQ4):c.803CCT[1] (p.Ser269del)]

NM_004700.4(KCNQ4):c.803CCT[1] (p.Ser269del)

Gene:

KCNQ4:potassium voltage-gated channel subfamily Q member 4 [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

1p34.2

Genomic location:

Preferred name:

NM_004700.4(KCNQ4):c.803CCT[1] (p.Ser269del)

HGVS:

NC_000001.10:g.41285111_41285113del
NC_000001.11:g.40819441CCT[1]
NG_008139.3:g.40655CCT[1]
NM_004700.3:c.806_808del
NM_004700.4:c.803CCT[1]MANE SELECT
NM_172163.3:c.803CCT[1]
NP_004691.2:p.Ser269del
NP_751895.1:p.Ser269del
LRG_1378t1:c.803CCT[1]
LRG_1378:g.40655CCT[1]
LRG_1378p1:p.Ser269del
NC_000001.10:g.41285111_41285113del
NC_000001.10:g.41285113CCT[1]
NC_000001.10:g.41285116_41285118delCCT
NC_000001.11:g.40819441_40819443CCT[1]
NM_004700.2:c.806_808delCCT
NM_004700.3:c.806_808delCCT
NM_004700.4(KCNQ4):c.803_805CCT[1]MANE SELECT

Protein change:

S269del

Links:

dbSNP: rs797044966

NCBI 1000 Genomes Browser:

rs797044966

Molecular consequence:

NM_004700.4:c.803CCT[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_172163.3:c.803CCT[1] - inframe_deletion - [Sequence Ontology: SO:0001822]

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
SCV000967428	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Uncertain significance (Feb 26, 2018)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 23443030, 23399560, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000967428

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Uncertain significance
(Feb 26, 2018)

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	not provided	2	2	not provided	not provided	not provided	clinical testing

Citations

PubMed

Identification of a novel in-frame deletion in KCNQ4 (DFNA2A) and evidence of multiple phenocopies of unknown origin in a family with ADSNHL.

Abdelfatah N, McComiskey DA, Doucette L, Griffin A, Moore SJ, Negrijn C, Hodgkinson KA, King JJ, Larijani M, Houston J, Stanton SG, Young TL.

Eur J Hum Genet. 2013 Oct;21(10):1112-9. doi: 10.1038/ejhg.2013.5. Epub 2013 Feb 27.

PubMed [citation]

PMID:: 23443030
PMCID:: PMC3778362

Moderate hearing loss associated with a novel KCNQ4 non-truncating mutation located near the N-terminus of the pore helix.

Watabe T, Matsunaga T, Namba K, Mutai H, Inoue Y, Ogawa K.

Biochem Biophys Res Commun. 2013 Mar 15;432(3):475-9. doi: 10.1016/j.bbrc.2013.01.118. Epub 2013 Feb 9.

PubMed [citation]

PMID:: 23399560

See all PubMed Citations (3)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000967428.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	PubMed (3)

Description

Variant classified as Uncertain Significance - Favor Pathogenic. The p.Ser269del variant in KCNQ4 has been reported in 2 individuals with bilateral sloping hear ing loss and segregated with disease in 9 affected relatives from 1 family (Wata be 2013, Abdelfatah 2013). However, there was one individual with a similar hear ing loss pattern and two additional individuals with other forms of hearing loss that did not harbor the variant, as well as 7 family members with hearing loss on the other side of the family that did not harbor the variant (Abdelfatah 2013 ). The p.Ser269del variant was absent from large population studies and is repor ted in ClinVar (Variation ID# 204595). This variant is a deletion of 1 amino aci d at position 269 and is not predicted to alter the protein reading-frame. In su mmary, while there is some suspicion for a pathogenic role, the clinical signifi cance of the p.Ser269del variant is uncertain. ACMG/AMP Criteria applied: PP1_St rong, PM2, PS4_Supporting, BS4.

#	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: Nov 24, 2024

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