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NM_000188.3(HK1):c.1370C>T (p.Thr457Met) AND Inborn genetic diseases

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Mar 5, 2020
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:
RCV001266327.5

Allele description [Variation Report for NM_000188.3(HK1):c.1370C>T (p.Thr457Met)]

NM_000188.3(HK1):c.1370C>T (p.Thr457Met)

Gene:
HK1:hexokinase 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
10q22.1
Genomic location:
Preferred name:
NM_000188.3(HK1):c.1370C>T (p.Thr457Met)
HGVS:
  • NC_000010.11:g.69382591C>T
  • NG_012077.1:g.117592C>T
  • NM_000188.3:c.1370C>TMANE SELECT
  • NM_001322364.2:c.1382C>T
  • NM_001322365.2:c.1475C>T
  • NM_001322366.1:c.1286C>T
  • NM_001322367.1:c.1274C>T
  • NM_001358263.1:c.1382C>T
  • NM_033496.3:c.1367C>T
  • NM_033497.3:c.1382C>T
  • NM_033498.3:c.1382C>T
  • NM_033500.2:c.1334C>T
  • NP_000179.2:p.Thr457Met
  • NP_000179.2:p.Thr457Met
  • NP_001309293.1:p.Thr461Met
  • NP_001309294.1:p.Thr492Met
  • NP_001309295.1:p.Thr429Met
  • NP_001309296.1:p.Thr425Met
  • NP_001345192.1:p.Thr461Met
  • NP_277031.1:p.Thr456Met
  • NP_277032.1:p.Thr461Met
  • NP_277032.1:p.Thr461Met
  • NP_277033.1:p.Thr461Met
  • NP_277035.2:p.Thr445Met
  • LRG_365t1:c.1334C>T
  • LRG_365:g.117592C>T
  • LRG_365p1:p.Thr445Met
  • NC_000010.10:g.71142347C>T
  • NM_000188.2:c.1370C>T
  • NM_033497.2:c.1382C>T
Protein change:
T425M; THR457MET
Links:
OMIM: 142600.0009; dbSNP: rs1057517928
NCBI 1000 Genomes Browser:
rs1057517928
Molecular consequence:
  • NM_000188.3:c.1370C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322364.2:c.1382C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322365.2:c.1475C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322366.1:c.1286C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322367.1:c.1274C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001358263.1:c.1382C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_033496.3:c.1367C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_033497.3:c.1382C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_033498.3:c.1382C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_033500.2:c.1334C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Inborn genetic diseases
Identifiers:
MeSH: D030342; MedGen: C0950123

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001444501Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely pathogenic
(Mar 5, 2020) 		germlineclinical testing

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

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

De novo variants in HK1 associated with neurodevelopmental abnormalities and visual impairment.

Okur V, Cho MT, van Wijk R, van Oirschot B, Picker J, Coury SA, Grange D, Manwaring L, Krantz I, Muraresku CC, Hulick PJ, May H, Pierce E, Place E, Bujakowska K, Telegrafi A, Douglas G, Monaghan KG, Begtrup A, Wilson A, Retterer K, Anyane-Yeboa K, et al.

Eur J Hum Genet. 2019 Jul;27(7):1081-1089. doi: 10.1038/s41431-019-0366-9. Epub 2019 Feb 18.

PubMed [citation]
PMID:
30778173
PMCID:
PMC6777464

Details of each submission

From Ambry Genetics, SCV001444501.4

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

Description

The alteration results in an amino acid change:_x000D_ _x000D_ The c.1370C>T (p.T457M) alteration is located in coding exon 10 of the HK1 gene. This alteration results from a C to T substitution at nucleotide position 1370, causing the threonine (T) at amino acid position 457 to be replaced by a methionine (M). The alteration is not observed in population databases: _x000D_ _x000D_ Based on data from the Genome Aggregation Database (gnomAD), the HK1 c.1370C>T alteration was not observed, with coverage at this position. The alteratione has been observed in affected individuals: _x000D_ _x000D_ This alteration was described to occur de novo in three individuals from two families with neurodevelopmental abnormalities. Common features included developmental delay, brain MRI anomalies, and optic atrophy. Additional issues included seizures, tone abnormalities, failure to thrive, swallowing and feeding difficulties, hearing loss, and laryngotracheomalacia (Okur, 2019). The altered amino acid is conserved throughout evolution:_x000D_ _x000D_ The p.T457 amino acid is conserved in available vertebrate species. The alteration is predicted tolerated by in silico modeling:_x000D_ _x000D_ The p.T457M alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, this alteration is classified as likely pathogenic.

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

Last Updated: Oct 13, 2024