NM_000188.3(HK1):c.1370C>T (p.Thr457Met) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Aug 1, 2020
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000413860.22

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]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000491089	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Likely pathogenic (May 17, 2016)	germline	clinical testing	Citation Link,
SCV001501992	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Aug 1, 2020)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000491089

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Likely pathogenic
(May 17, 2016)

germline

clinical testing

Citation Link,

SCV001501992

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Pathogenic
(Aug 1, 2020)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	2	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From GeneDx, SCV000491089.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The T457M variant in the HK1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The T457M variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The T457M variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. The T457M variant is a strong candidate for a pathogenic variant.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From CeGaT Center for Human Genetics Tuebingen, SCV001501992.22

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		2	not provided	not provided	not provided

Last Updated: Oct 13, 2024

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