Submissions for variant NM_021830.5(TWNK):c.2050A>C (p.Lys684Gln)

gnomAD frequency: 0.00009  dbSNP: rs369223258

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001722382	SCV000329172	likely benign	not provided	2021-01-06	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000278667	SCV000359951	likely benign	Progressive external ophthalmoplegia with mitochondrial DNA deletions	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000352301	SCV000359952	likely benign	Ataxia Neuropathy Spectrum Disorders	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000406261	SCV000359953	likely benign	Autosomal recessive cerebellar ataxia	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000312773	SCV000359954	likely benign	Mitochondrial DNA depletion syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV001336025	SCV001529302	uncertain significance	Infantile onset spinocerebellar ataxia	2018-10-15	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001848044	SCV002106285	uncertain significance	Hereditary spastic paraplegia	2017-10-02	criteria provided, single submitter	clinical testing
Invitae	RCV001722382	SCV002110351	uncertain significance	not provided	2023-12-20	criteria provided, single submitter	clinical testing	This sequence change replaces lysine, which is basic and polar, with glutamine, which is neutral and polar, at codon 684 of the TWNK protein (p.Lys684Gln). This variant is present in population databases (rs369223258, gnomAD 0.01%). This missense change has been observed in individual(s) with autism spectrum disorder (PMID: 35982159). ClinVar contains an entry for this variant (Variation ID: 279716). 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 TWNK protein function with a negative predictive value of 95%. 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.
Mayo Clinic Laboratories, Mayo Clinic	RCV001722382	SCV004225321	uncertain significance	not provided	2022-04-18	criteria provided, single submitter	clinical testing	BP4
Ambry Genetics	RCV004021053	SCV004974181	uncertain significance	Inborn genetic diseases	2021-06-18	criteria provided, single submitter	clinical testing	The c.2050A>C (p.K684Q) alteration is located in exon 5 (coding exon 5) of the C10orf2 gene. This alteration results from a A to C substitution at nucleotide position 2050, causing the lysine (K) at amino acid position 684 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.