ClinVar Miner

Submissions for variant NM_017777.4(MKS1):c.638A>G (p.Tyr213Cys)

gnomAD frequency: 0.00001  dbSNP: rs754689401
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001318231 SCV001508924 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome 2024-02-12 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 213 of the MKS1 protein (p.Tyr213Cys). This variant is present in population databases (rs754689401, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with MKS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1018871). 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 MKS1 protein function with a negative 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.
GeneDx RCV002511077 SCV002820540 uncertain significance not provided 2022-07-15 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Natera, Inc. RCV001830311 SCV002087650 uncertain significance Meckel syndrome, type 1 2021-04-27 no assertion criteria provided clinical testing

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