NM_001365951.3(KIF1B):c.2159C>T (p.Thr720Ile) AND Charcot-Marie-Tooth disease, type 2

Clinical significance:Uncertain significance (Last evaluated: Jul 13, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000467791.6

Allele description [Variation Report for NM_001365951.3(KIF1B):c.2159C>T (p.Thr720Ile)]

NM_001365951.3(KIF1B):c.2159C>T (p.Thr720Ile)

Gene:
KIF1B:kinesin family member 1B [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1p36.22
Genomic location:
Preferred name:
NM_001365951.3(KIF1B):c.2159C>T (p.Thr720Ile)
HGVS:
  • NC_000001.11:g.10320086C>T
  • NG_008069.1:g.114381C>T
  • NM_001365951.3:c.2159C>TMANE SELECT
  • NM_001365952.1:c.2159C>T
  • NM_015074.3:c.2021C>T
  • NP_001352880.1:p.Thr720Ile
  • NP_001352881.1:p.Thr720Ile
  • NP_055889.2:p.Thr674Ile
  • LRG_252t1:c.2021C>T
  • LRG_252t2:c.2159C>T
  • LRG_252:g.114381C>T
  • LRG_252p1:p.Thr674Ile
  • LRG_252p2:p.Thr720Ile
  • NC_000001.10:g.10380144C>T
  • p.Thr674Ile
Protein change:
T674I
Links:
dbSNP: rs41274468
NCBI 1000 Genomes Browser:
rs41274468
Molecular consequence:
  • NM_001365951.3:c.2159C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365952.1:c.2159C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_015074.3:c.2021C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Charcot-Marie-Tooth disease, type 2
Synonyms:
Charcot-Marie-Tooth, Type 2
Identifiers:
MONDO: MONDO:0018993; MedGen: C0270914

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000547914Invitaecriteria provided, single submitter
Uncertain significance
(Jul 13, 2020)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Pathogenic variant burden in the ExAC database: an empirical approach to evaluating population data for clinical variant interpretation.

Kobayashi Y, Yang S, Nykamp K, Garcia J, Lincoln SE, Topper SE.

Genome Med. 2017 Feb 6;9(1):13. doi: 10.1186/s13073-017-0403-7.

PubMed [citation]
PMID:
28166811
PMCID:
PMC5295186

Phenotype risk scores identify patients with unrecognized Mendelian disease patterns.

Bastarache L, Hughey JJ, Hebbring S, Marlo J, Zhao W, Ho WT, Van Driest SL, McGregor TL, Mosley JD, Wells QS, Temple M, Ramirez AH, Carroll R, Osterman T, Edwards T, Ruderfer D, Velez Edwards DR, Hamid R, Cogan J, Glazer A, Wei WQ, Feng Q, et al.

Science. 2018 Mar 16;359(6381):1233-1239. doi: 10.1126/science.aal4043.

PubMed [citation]
PMID:
29590070
PMCID:
PMC5959723
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000547914.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces threonine with isoleucine at codon 674 of the KIF1B protein (p.Thr674Ile). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is present in population databases (rs41274468, ExAC 0.01%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been observed in several individuals affected with Charcot-Marie-Tooth disease (PMID: 29590070). ClinVar contains an entry for this variant (Variation ID: 408312). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: Tolerated; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). 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.

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

Last Updated: Dec 2, 2021

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