NM_001199107.2(TBC1D24):c.321T>A (p.Asn107Lys) AND multiple conditions

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jun 10, 2023
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:: RCV001049900.8

Allele description [Variation Report for NM_001199107.2(TBC1D24):c.321T>A (p.Asn107Lys)]

NM_001199107.2(TBC1D24):c.321T>A (p.Asn107Lys)

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.321T>A (p.Asn107Lys)

HGVS:

NC_000016.10:g.2496469T>A
NG_028170.1:g.26324T>A
NM_001199107.2:c.321T>AMANE SELECT
NM_020705.3:c.321T>A
NP_001186036.1:p.Asn107Lys
NP_065756.1:p.Asn107Lys
NC_000016.9:g.2546470T>A
NM_001199107.1:c.321T>A

Protein change:

N107K

Links:

dbSNP: rs1057524192

NCBI 1000 Genomes Browser:

rs1057524192

Molecular consequence:

NM_001199107.2:c.321T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_020705.3:c.321T>A - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001213974	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jun 10, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 27502353, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001213974

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jun 10, 2023)

germline

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

Citations

PubMed

Electroclinical phenotypes and outcomes in TBC1D24-related epilepsy.

Appavu B, Guido-Estrada N, Lindstrom K, Grebe T, Kerrigan JF, Troester M.

Epileptic Disord. 2016 Sep 1;18(3):324-8. doi: 10.1684/epd.2016.0849.

PubMed [citation]

PMID:: 27502353

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, SCV001213974.5

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

Description

This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 107 of the TBC1D24 protein (p.Asn107Lys). This variant is not present in population databases (gnomAD no frequency). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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 not expected to disrupt TBC1D24 protein function. ClinVar contains an entry for this variant (Variation ID: 391688). This missense change has been observed in individual(s) with autosomal recessive TBC1D24-related epilepsy (PMID: 27502353). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant.

#	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

Last Updated: Sep 29, 2024

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