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NM_001393500.2(TOMT):c.100C>T (p.Arg34Ter) AND Autosomal recessive nonsyndromic hearing loss 63

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 6, 2021
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:
RCV002471368.1

Allele description [Variation Report for NM_001393500.2(TOMT):c.100C>T (p.Arg34Ter)]

NM_001393500.2(TOMT):c.100C>T (p.Arg34Ter)

Genes:
LRTOMT:leucine rich transmembrane and O-methyltransferase domain containing [Gene - OMIM - HGNC]
TOMT:transmembrane O-methyltransferase [Gene - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11q13.4
Genomic location:
Preferred name:
NM_001393500.2(TOMT):c.100C>T (p.Arg34Ter)
HGVS:
  • NC_000011.10:g.72106051C>T
  • NG_021423.1:g.30716C>T
  • NM_001145308.5:c.199C>T
  • NM_001145309.4:c.199C>T
  • NM_001145310.4:c.84-5C>T
  • NM_001393500.2:c.100C>TMANE SELECT
  • NP_001138780.1:p.Arg67Ter
  • NP_001138780.1:p.Arg67Ter
  • NP_001138781.1:p.Arg67Ter
  • NP_001380429.1:p.Arg34Ter
  • NC_000011.9:g.71817097C>T
  • NM_001145308.4:c.199C>T
Protein change:
R34*
Molecular consequence:
  • NM_001145310.4:c.84-5C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001145308.5:c.199C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001145309.4:c.199C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001393500.2:c.100C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Autosomal recessive nonsyndromic hearing loss 63
Synonyms:
Deafness, autosomal recessive 63
Identifiers:
MONDO: MONDO:0012670; MedGen: C1969621; Orphanet: 90636; OMIM: 611451

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002767354Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(May 6, 2021) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

A catechol-O-methyltransferase that is essential for auditory function in mice and humans.

Du X, Schwander M, Moresco EM, Viviani P, Haller C, Hildebrand MS, Pak K, Tarantino L, Roberts A, Richardson H, Koob G, Najmabadi H, Ryan AF, Smith RJ, Müller U, Beutler B.

Proc Natl Acad Sci U S A. 2008 Sep 23;105(38):14609-14. doi: 10.1073/pnas.0807219105. Epub 2008 Sep 15.

PubMed [citation]
PMID:
18794526
PMCID:
PMC2567147

Mutations of LRTOMT, a fusion gene with alternative reading frames, cause nonsyndromic deafness in humans.

Ahmed ZM, Masmoudi S, Kalay E, Belyantseva IA, Mosrati MA, Collin RW, Riazuddin S, Hmani-Aifa M, Venselaar H, Kawar MN, Tlili A, van der Zwaag B, Khan SY, Ayadi L, Riazuddin SA, Morell RJ, Griffith AJ, Charfedine I, Caylan R, Oostrik J, Karaguzel A, Ghorbel A, et al.

Nat Genet. 2008 Nov;40(11):1335-40. doi: 10.1038/ng.245. Epub 2008 Oct 26.

PubMed [citation]
PMID:
18953341
PMCID:
PMC3404732
See all PubMed Citations (4)

Details of each submission

From Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV002767354.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with deafness (MIM#611451). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0219 - This variant is non-coding in an alternative transcript. This gene encodes two structurally unrelated proteins, LRTOMT1 and LRTOMT2 (PMID: 18953341). This variant is non-coding in LRTOMT1. (I) 0252 - This variant is homozygous. (I) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (1 heterozygote, 0 homozygotes). (SP) 0702 - Other NMD-predicted variants comparable to the one identified in this case have strong previous evidence for pathogenicity. NMD-predicted variants have been reported in multiple individuals with autosomal recessive deafness (ClinVar, PMID: 18953341, 18794526, 21739586). (SP) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Dec 24, 2022