ClinVar Miner

Submissions for variant NM_001199397.3(NEK1):c.3727G>T (p.Asp1243Tyr)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV002510081 SCV002818847 uncertain significance not provided 2022-09-15 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Invitae RCV003635994 SCV004445631 uncertain significance Short-rib thoracic dysplasia 6 with or without polydactyly 2023-12-15 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 1215 of the NEK1 protein (p.Asp1215Tyr). This variant is present in population databases (rs542986015, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with NEK1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1810594). 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 NEK1 protein function with a positive predictive value of 80%. 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.
PreventionGenetics, part of Exact Sciences RCV003926399 SCV004738932 likely benign NEK1-related disorder 2023-11-16 criteria provided, single submitter clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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