ClinVar Miner

Submissions for variant NM_021830.5(TWNK):c.1321T>G (p.Trp441Gly)

gnomAD frequency: 0.00001  dbSNP: rs672601361
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV003556197 SCV004295691 pathogenic not provided 2023-07-10 criteria provided, single submitter clinical testing This sequence change replaces tryptophan, which is neutral and slightly polar, with glycine, which is neutral and non-polar, at codon 441 of the TWNK protein (p.Trp441Gly). This variant is present in population databases (rs672601361, gnomAD 0.0009%). This missense change has been observed in individual(s) with autosomal recessive Perrault syndrome (PMID: 25355836). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 162050). 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. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000149472 SCV000196116 pathogenic Perrault syndrome 5 2014-11-25 no assertion criteria provided literature only
GeneReviews RCV002516007 SCV003525962 not provided Perrault syndrome no assertion provided literature only

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