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

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Dec 12, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:

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

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

KIF1B:kinesin family member 1B [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_001365951.3(KIF1B):c.2159C>T (p.Thr720Ile)
  • 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:
dbSNP: rs41274468
NCBI 1000 Genomes Browser:
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]


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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Dec 12, 2023)
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



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]

Comprehensive genetic sequence and copy number analysis for Charcot-Marie-Tooth disease in a Canadian cohort of 2517 patients.

Volodarsky M, Kerkhof J, Stuart A, Levy M, Brady LI, Tarnopolsky M, Lin H, Ainsworth P, Sadikovic B.

J Med Genet. 2021 Apr;58(4):284-288. doi: 10.1136/jmedgenet-2019-106641. Epub 2020 May 6.

PubMed [citation]
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000547914.9

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


This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 674 of the KIF1B protein (p.Thr674Ile). This variant is present in population databases (rs41274468, gnomAD 0.03%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 29590070, 32376792). ClinVar contains an entry for this variant (Variation ID: 408312). 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 KIF1B protein function with a negative predictive value of 80%. 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.

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

Last Updated: Jul 15, 2024