NM_005422.4(TECTA):c.3743C>T (p.Pro1248Leu) AND Autosomal recessive nonsyndromic hearing loss 21

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Oct 1, 2021
Review status:: criteria provided, conflicting classifications

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:: RCV001106728.7

Allele description [Variation Report for NM_005422.4(TECTA):c.3743C>T (p.Pro1248Leu)]

NM_005422.4(TECTA):c.3743C>T (p.Pro1248Leu)

Genes:

TBCEL-TECTA:TBCEL-TECTA readthrough [Gene - HGNC]
TECTA:tectorin alpha [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q23.3

Genomic location:

Preferred name:

NM_005422.4(TECTA):c.3743C>T (p.Pro1248Leu)

HGVS:

NC_000011.10:g.121145754C>T
NG_011633.1:g.48089C>T
NM_001378761.1:c.4700C>T
NM_005422.4:c.3743C>TMANE SELECT
NP_001365690.1:p.Pro1567Leu
NP_005413.2:p.Pro1248Leu
NP_005413.2:p.Pro1248Leu
NC_000011.9:g.121016463C>T
NM_005422.2:c.3743C>T

Protein change:

P1248L

Links:

dbSNP: rs138768918

NCBI 1000 Genomes Browser:

rs138768918

Molecular consequence:

NM_001378761.1:c.4700C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_005422.4:c.3743C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Autosomal recessive nonsyndromic hearing loss 21
Synonyms:: Deafness, autosomal recessive 21
Identifiers:: MONDO: MONDO:0011351; MedGen: C1863655; Orphanet: 90636; OMIM: 603629

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001263823	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Uncertain significance (Apr 28, 2017)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 21520338, 27068579, 25262649, 24586623 Citation Link,
SCV001976971	Laboratory of Medical Genetics, National & Kapodistrian University of Athens	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 1, 2021)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 34008892, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001263823

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Uncertain significance
(Apr 28, 2017)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link,

SCV001976971

Laboratory of Medical Genetics, National & Kapodistrian University of Athens

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Oct 1, 2021)

unknown

clinical testing

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	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

DFNA8/12 caused by TECTA mutations is the most identified subtype of nonsyndromic autosomal dominant hearing loss.

Hildebrand MS, Morín M, Meyer NC, Mayo F, Modamio-Hoybjor S, Mencía A, Olavarrieta L, Morales-Angulo C, Nishimura CJ, Workman H, DeLuca AP, del Castillo I, Taylor KR, Tompkins B, Goodman CW, Schrauwen I, Wesemael MV, Lachlan K, Shearer AE, Braun TA, Huygen PL, Kremer H, et al.

Hum Mutat. 2011 Jul;32(7):825-34. doi: 10.1002/humu.21512. Epub 2011 Jun 7.

PubMed [citation]

PMID:: 21520338
PMCID:: PMC3326665

DNA Diagnostics of Hereditary Hearing Loss: A Targeted Resequencing Approach Combined with a Mutation Classification System.

Sommen M, Schrauwen I, Vandeweyer G, Boeckx N, Corneveaux JJ, van den Ende J, Boudewyns A, De Leenheer E, Janssens S, Claes K, Verstreken M, Strenzke N, Predöhl F, Wuyts W, Mortier G, Bitner-Glindzicz M, Moser T, Coucke P, Huentelman MJ, Van Camp G.

Hum Mutat. 2016 Aug;37(8):812-9. doi: 10.1002/humu.22999. Epub 2016 May 6.

PubMed [citation]

PMID:: 27068579

See all PubMed Citations (6)

Details of each submission

From Illumina Laboratory Services, Illumina, SCV001263823.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

#	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

From Laboratory of Medical Genetics, National & Kapodistrian University of Athens, SCV001976971.1

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

Description

PM2, PP2, PP3, PP4, PP5

#	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: Oct 13, 2024

ClinVar

Relating variation to medicine