NM_001244008.2(KIF1A):c.223C>T (p.Arg75Trp) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 13, 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:: RCV000639785.7

Allele description [Variation Report for NM_001244008.2(KIF1A):c.223C>T (p.Arg75Trp)]

NM_001244008.2(KIF1A):c.223C>T (p.Arg75Trp)

Gene:

KIF1A:kinesin family member 1A [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q37.3

Genomic location:

Preferred name:

NM_001244008.2(KIF1A):c.223C>T (p.Arg75Trp)

HGVS:

NC_000002.12:g.240788191G>A
NG_029724.1:g.37017C>T
NM_001244008.2:c.223C>TMANE SELECT
NM_001320705.2:c.223C>T
NM_001330289.2:c.223C>T
NM_001330290.2:c.223C>T
NM_001379631.1:c.223C>T
NM_001379632.1:c.223C>T
NM_001379633.1:c.223C>T
NM_001379634.1:c.223C>T
NM_001379635.1:c.223C>T
NM_001379636.1:c.223C>T
NM_001379637.1:c.223C>T
NM_001379638.1:c.223C>T
NM_001379639.1:c.223C>T
NM_001379640.1:c.223C>T
NM_001379641.1:c.223C>T
NM_001379642.1:c.223C>T
NM_001379645.1:c.223C>T
NM_001379646.1:c.223C>T
NM_001379648.1:c.223C>T
NM_001379649.1:c.223C>T
NM_001379650.1:c.223C>T
NM_001379651.1:c.223C>T
NM_001379653.1:c.223C>T
NM_004321.8:c.223C>T
NP_001230937.1:p.Arg75Trp
NP_001230937.1:p.Arg75Trp
NP_001307634.1:p.Arg75Trp
NP_001317218.1:p.Arg75Trp
NP_001317219.1:p.Arg75Trp
NP_001366560.1:p.Arg75Trp
NP_001366561.1:p.Arg75Trp
NP_001366562.1:p.Arg75Trp
NP_001366563.1:p.Arg75Trp
NP_001366564.1:p.Arg75Trp
NP_001366565.1:p.Arg75Trp
NP_001366566.1:p.Arg75Trp
NP_001366567.1:p.Arg75Trp
NP_001366568.1:p.Arg75Trp
NP_001366569.1:p.Arg75Trp
NP_001366570.1:p.Arg75Trp
NP_001366571.1:p.Arg75Trp
NP_001366574.1:p.Arg75Trp
NP_001366575.1:p.Arg75Trp
NP_001366577.1:p.Arg75Trp
NP_001366578.1:p.Arg75Trp
NP_001366579.1:p.Arg75Trp
NP_001366580.1:p.Arg75Trp
NP_001366582.1:p.Arg75Trp
NP_004312.2:p.Arg75Trp
NP_004312.2:p.Arg75Trp
LRG_367t1:c.223C>T
LRG_367t2:c.223C>T
LRG_367:g.37017C>T
LRG_367p1:p.Arg75Trp
LRG_367p2:p.Arg75Trp
NC_000002.11:g.241727608G>A
NM_001244008.1:c.223C>T
NM_004321.6:c.223C>T
NM_004321.7:c.223C>T

Protein change:

R75W

Links:

dbSNP: rs778224699

NCBI 1000 Genomes Browser:

rs778224699

Molecular consequence:

NM_001244008.2:c.223C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001320705.2:c.223C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001330289.2:c.223C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001330290.2:c.223C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379631.1:c.223C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379632.1:c.223C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379633.1:c.223C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379634.1:c.223C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379635.1:c.223C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379636.1:c.223C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379637.1:c.223C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379638.1:c.223C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379639.1:c.223C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379640.1:c.223C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379641.1:c.223C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379642.1:c.223C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379645.1:c.223C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379646.1:c.223C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379648.1:c.223C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379649.1:c.223C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379650.1:c.223C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379651.1:c.223C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379653.1:c.223C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_004321.8:c.223C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary spastic paraplegia 30
Synonyms:: Spastic paraplegia 30, autosomal recessive; SPASTIC PARAPLEGIA 30A, AUTOSOMAL DOMINANT
Identifiers:: MONDO: MONDO:0012476; MedGen: C5235139; Orphanet: 101010; OMIM: 610357

Name:: Neuropathy, hereditary sensory, type 2C
Synonyms:: Hereditary sensory and autonomic neuropathy type IIC
Identifiers:: MONDO: MONDO:0013634; MedGen: C3280168; Orphanet: 970; OMIM: 614213

Name:: Intellectual disability, autosomal dominant 9 (NESCAVS)
Synonyms:: Mental retardation, autosomal dominant 9; NESCAV SYNDROME
Identifiers:: MONDO: MONDO:0013656; MedGen: C5393830; OMIM: 614255

Recent activity

Clear Turn Off Turn On

LFNG [Trachypithecus francoisi]
LFNG [Trachypithecus francoisi]
Gene ID:117072008

Gene

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000761366	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 13, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 27124789, 33717719, 33753861, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000761366

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 13, 2023)

germline

clinical testing

PubMed (4)
[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

Clinical genomics can facilitate countrywide estimation of autosomal recessive disease burden.

Abouelhoda M, Sobahy T, El-Kalioby M, Patel N, Shamseldin H, Monies D, Al-Tassan N, Ramzan K, Imtiaz F, Shaheen R, Alkuraya FS.

Genet Med. 2016 Dec;18(12):1244-1249. doi: 10.1038/gim.2016.37. Epub 2016 Apr 28.

PubMed [citation]

PMID:: 27124789

A Novel Synergistic Association of Variants in PTRH2 and KIF1A Relates to a Syndrome of Hereditary Axonopathy, Outer Hair Cell Dysfunction, Intellectual Disability, Pancreatic Lipomatosis, Diabetes, Cerebellar Atrophy, and Vertebral Artery Hypoplasia.

Charles Bronson S, Suresh E, Stephen Abraham Suresh Kumar S, Mythili C, Shanmugam A.

Cureus. 2021 Feb 6;13(2):e13174. doi: 10.7759/cureus.13174.

PubMed [citation]

PMID:: 33717719
PMCID:: PMC7939034

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000761366.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 75 of the KIF1A protein (p.Arg75Trp). This variant is present in population databases (rs778224699, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features of KIF1A-related conditions (PMID: 27124789, 33717719, 33753861). ClinVar contains an entry for this variant (Variation ID: 191158). 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 KIF1A protein function. 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.

#	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: Oct 13, 2024

ClinVar

Relating variation to medicine