VCV000548564.11 - ClinVar

NM_018706.7(DHTKD1):c.1792C>T (p.Arg598Cys)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Uncertain significance
Uncertain significance (4)

4 out of 4 submissions contributed to this classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_018706.7(DHTKD1):c.1792C>T (p.Arg598Cys)

Variation ID: 548564 Accession: VCV000548564.11

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 10p14 10: 12101077 (GRCh38) [ NCBI UCSC ] 10: 12143076 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Jul 13, 2018	Feb 23, 2026	Nov 13, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_018706.7:c.1792C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_061176.4:p.Arg598Cys	missense
NM_018706.5:c.1792C>T
NC_000010.11:g.12101077C>T
NC_000010.10:g.12143076C>T
NG_033248.1:g.37161C>T

... more HGVS ... less HGVS

Protein change

R598C

Other names

Canonical SPDI

NC_000010.11:12101076:C:T

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD) 0.00002

Trans-Omics for Precision Medicine (TOPMed) 0.00003

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008

Links

ClinGen: CA202587887 dbSNP: rs375292909 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
DHTKD1		-	-	GRCh38 GRCh37	1060	1124

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Charcot-Marie-Tooth disease axonal type 2Q	Uncertain significance (1)	criteria provided, single submitter	Mar 5, 2018	RCV000662099.5
2-aminoadipic 2-oxoadipic aciduria	Uncertain significance (2)	criteria provided, multiple submitters, no conflicts	Sep 2, 2024	RCV000662100.9
Inborn genetic diseases	Uncertain significance (1)	criteria provided, single submitter	Nov 13, 2025	RCV003163049.3

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Uncertain significance (Mar 05, 2018) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Charcot-Marie-Tooth disease axonal type 2Q	Genomic Research Center, Shahid Beheshti University of Medical Sciences Accession: SCV000784439.3 First in ClinVar: Jul 13, 2018 Last updated: Apr 13, 2025	Observation: 1 Collection method: clinical testing Allele origin: inherited Affected status: yes more Observation 1 Collection method: clinical testing Allele origin: inherited Affected status: yes Number of individuals with the variant: 1 Age: 0-9 years Sex: male Geographic origin: Iran

Uncertain significance (Mar 05, 2018) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	2-aminoadipic 2-oxoadipic aciduria	Genomic Research Center, Shahid Beheshti University of Medical Sciences Accession: SCV000784440.3 First in ClinVar: Jul 13, 2018 Last updated: Apr 13, 2025	Observation: 1 Collection method: clinical testing Allele origin: inherited Affected status: yes more Observation 1 Collection method: clinical testing Allele origin: inherited Affected status: yes Number of individuals with the variant: 1 Age: 0-9 years Sex: male Geographic origin: Iran

Uncertain significance (Nov 13, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Inborn genetic diseases	Ambry Genetics Accession: SCV003891902.3 First in ClinVar: Apr 15, 2023 Last updated: Jan 11, 2026	Comment: show The c.1792C>T (p.R598C) alteration is located in exon 10 (coding exon 10) of the DHTKD1 gene. This alteration results from a C to T substitution at nucleotide position 1792, causing the arginine (R) at amino acid position 598 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Uncertain significance (Sep 02, 2024) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	2-aminoadipic 2-oxoadipic aciduria	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV004276410.3 First in ClinVar: Feb 14, 2024 Last updated: Feb 23, 2026	Comment: show This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 598 of the DHTKD1 protein (p.Arg598Cys). This variant is present in population databases (rs375292909, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with DHTKD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 548564). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt DHTKD1 protein function with a positive 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. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Comment:

The c.1792C>T (p.R598C) alteration is located in exon 10 (coding exon 10) of the DHTKD1 gene. This alteration results from a C to T substitution at nucleotide position 1792, causing the arginine (R) at amino acid position 598 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

Comment:

This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 598 of the DHTKD1 protein (p.Arg598Cys). This variant is present in population databases (rs375292909, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with DHTKD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 548564). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt DHTKD1 protein function with a positive 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.

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs375292909 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Apr 13, 2026