Submissions for variant NM_018706.7(DHTKD1):c.2747A>G (p.Lys916Arg)

gnomAD frequency: 0.00001  dbSNP: rs1016086446

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Baylor Genetics	RCV001331064	SCV001522984	uncertain significance	2-aminoadipic 2-oxoadipic aciduria	2019-01-07	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Labcorp Genetics (formerly Invitae), Labcorp	RCV001331064	SCV003261020	uncertain significance	2-aminoadipic 2-oxoadipic aciduria	2021-12-23	criteria provided, single submitter	clinical testing	This variant is not present in population databases (gnomAD no frequency). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 585057). This variant has not been reported in the literature in individuals affected with DHTKD1-related conditions. This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 916 of the DHTKD1 protein (p.Lys916Arg).
Ambry Genetics	RCV002532896	SCV003581167	uncertain significance	Inborn genetic diseases	2021-09-15	criteria provided, single submitter	clinical testing	The c.2747A>G (p.K916R) alteration is located in exon 17 (coding exon 17) of the DHTKD1 gene. This alteration results from a A to G substitution at nucleotide position 2747, causing the lysine (K) at amino acid position 916 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GenomeConnect, ClinGen	RCV000709811	SCV000840139	not provided	2-aminoadipic 2-oxoadipic aciduria; Charcot-Marie-Tooth disease axonal type 2Q		no assertion provided	phenotyping only	GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
GenomeConnect - Brain Gene Registry	RCV001331064	SCV004804598	not provided	2-aminoadipic 2-oxoadipic aciduria		no assertion provided	phenotyping only	Variant classified as Uncertain significance and reported on 01-07-2019 by Baylor Genetics. Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect does not attempt to reinterpret the variant. The IDDRC-CTSA National Brain Gene Registry (BGR) is a study funded by the U.S. National Center for Advancing Translational Sciences (NCATS) and includes 13 Intellectual and Developmental Disability Research Center (IDDRC) institutions. The study is led by Principal Investigator Dr. Philip Payne from Washington University. The BGR is a data commons of gene variants paired with subject clinical information. This database helps scientists learn more about genetic changes and their impact on the brain and behavior. Participation in the Brain Gene Registry requires participation in GenomeConnect. More information about the Brain Gene Registry can be found on the study website - https://braingeneregistry.wustl.edu/.