ClinVar Miner

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

gnomAD frequency: 0.00009  dbSNP: rs369223258
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Total submissions: 9
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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

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