ClinVar Miner

Submissions for variant NM_021830.5(TWNK):c.1172G>A (p.Arg391His)

gnomAD frequency: 0.00001  dbSNP: rs556445621
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000290037 SCV000359911 likely benign Infantile onset spinocerebellar ataxia 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina RCV000345001 SCV000359912 likely benign Autosomal recessive cerebellar ataxia 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina RCV000403533 SCV000359913 likely benign Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina RCV000305281 SCV000359914 likely benign Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Invitae RCV002516005 SCV003262616 pathogenic not provided 2024-01-16 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 391 of the TWNK protein (p.Arg391His). This variant is present in population databases (rs556445621, gnomAD 0.05%). This missense change has been observed in individuals with autosomal recessive TWNK-related conditions (PMID: 25355836, 32619254, 33095980). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 162048). 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 expected to disrupt TWNK protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity RCV002516005 SCV003827959 uncertain significance not provided 2022-07-21 criteria provided, single submitter clinical testing
OMIM RCV000149470 SCV000196114 pathogenic Perrault syndrome 5 2014-11-25 no assertion criteria provided literature only
GeneReviews RCV002516006 SCV003525960 not provided Perrault syndrome no assertion provided literature only

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