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NM_001199107.2(TBC1D24):c.746A>T (p.Lys249Met) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
May 25, 2022
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:
RCV002634290.3

Allele description [Variation Report for NM_001199107.2(TBC1D24):c.746A>T (p.Lys249Met)]

NM_001199107.2(TBC1D24):c.746A>T (p.Lys249Met)

Gene:
TBC1D24:TBC1 domain family member 24 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
16p13.3
Genomic location:
Preferred name:
NM_001199107.2(TBC1D24):c.746A>T (p.Lys249Met)
HGVS:
  • NC_000016.10:g.2496894A>T
  • NG_028170.1:g.26749A>T
  • NG_132773.1:g.179A>T
  • NM_001199107.2:c.746A>TMANE SELECT
  • NM_020705.3:c.746A>T
  • NP_001186036.1:p.Lys249Met
  • NP_065756.1:p.Lys249Met
  • NC_000016.9:g.2546895A>T
Protein change:
K249M
Molecular consequence:
  • NM_001199107.2:c.746A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_020705.3:c.746A>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Developmental and epileptic encephalopathy, 1 (DEE1)
Synonyms:
INFANTILE SPASM SYNDROME, X-LINKED 1; X-linked infantile spasms; West's syndrome; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0010632; MedGen: C3463992; OMIM: 308350
Name:
Autosomal dominant nonsyndromic hearing loss 65
Synonyms:
Deafness, autosomal dominant 65
Identifiers:
MONDO: MONDO:0014470; MedGen: C3892048; Orphanet: 90635; OMIM: 616044
Name:
Caused by mutation in the TBC1 domain family, member 24
Identifiers:
MedGen: CN236805

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003523277Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(May 25, 2022) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003523277.2

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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 TBC1D24 protein function. This variant has not been reported in the literature in individuals affected with TBC1D24-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with methionine, which is neutral and non-polar, at codon 249 of the TBC1D24 protein (p.Lys249Met).

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

Last Updated: Sep 29, 2024