NM_018706.7(DHTKD1):c.1118C>T (p.Pro373Leu) AND 2-aminoadipic 2-oxoadipic aciduria

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Aug 25, 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:: RCV001250095.4

Allele description [Variation Report for NM_018706.7(DHTKD1):c.1118C>T (p.Pro373Leu)]

NM_018706.7(DHTKD1):c.1118C>T (p.Pro373Leu)

Gene:

DHTKD1:dehydrogenase E1 and transketolase domain containing 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10p14

Genomic location:

Preferred name:

NM_018706.7(DHTKD1):c.1118C>T (p.Pro373Leu)

HGVS:

NC_000010.11:g.12091643C>T
NG_033248.1:g.27727C>T
NM_018706.7:c.1118C>TMANE SELECT
NP_061176.4:p.Pro373Leu
NC_000010.10:g.12133642C>T
NC_000010.10:g.12133642C>T
NM_018706.3:c.1118C>T

Protein change:

P373L

Links:

dbSNP: rs556384043

NCBI 1000 Genomes Browser:

rs556384043

Molecular consequence:

NM_018706.7:c.1118C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: 2-aminoadipic 2-oxoadipic aciduria (AAKAD)
Synonyms:: Aminoadipic aciduria; ALPHA-AMINOADIPIC AND ALPHA-KETOADIPIC ACIDURIA
Identifiers:: MONDO: MONDO:0008774; MedGen: C1859817; Orphanet: 79154; OMIM: 204750

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001424282	Elsea Laboratory, Baylor College of Medicine	no assertion criteria provided	Likely pathogenic (Apr 1, 2020)	maternal, paternal	clinical testing
SCV004685806	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 25, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001424282

Elsea Laboratory, Baylor College of Medicine

no assertion criteria provided

Likely pathogenic
(Apr 1, 2020)

maternal, paternal

clinical testing

SCV004685806

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 25, 2023)

germline

clinical testing

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

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
not provided	maternal	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	paternal	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Elsea Laboratory, Baylor College of Medicine, SCV001424282.1

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004685806.1

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

Description

Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. 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 DHTKD1 protein function. This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 373 of the DHTKD1 protein (p.Pro373Leu). This variant is present in population databases (rs556384043, gnomAD 0.005%). 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: 973472).

#	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: Sep 29, 2024

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