ClinVar Miner

Submissions for variant NM_017777.4(MKS1):c.1363G>C (p.Glu455Gln)

gnomAD frequency: 0.00019  dbSNP: rs199927741
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000284786 SCV000333770 uncertain significance not provided 2018-04-17 criteria provided, single submitter clinical testing
GeneDx RCV000284786 SCV001982070 uncertain significance not provided 2021-09-15 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function
Labcorp Genetics (formerly Invitae), Labcorp RCV001855102 SCV002143123 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome 2022-06-13 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 455 of the MKS1 protein (p.Glu455Gln). This variant is present in population databases (rs199927741, gnomAD 0.07%). 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: 282351). 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 MKS1 protein function. 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.
Ambry Genetics RCV002519110 SCV003724306 uncertain significance Inborn genetic diseases 2021-01-13 criteria provided, single submitter clinical testing The c.1363G>C (p.E455Q) alteration is located in exon 15 (coding exon 15) of the MKS1 gene. This alteration results from a G to C substitution at nucleotide position 1363, causing the glutamic acid (E) at amino acid position 455 to be replaced by a glutamine (Q). The in silico prediction for the p.E455Q alteration is inconclusive. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV005025418 SCV005647321 uncertain significance Bardet-Biedl syndrome 13; Meckel syndrome, type 1; Joubert syndrome 28 2024-05-31 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004529461 SCV004111838 uncertain significance MKS1-related disorder 2024-04-09 no assertion criteria provided clinical testing The MKS1 c.1363G>C variant is predicted to result in the amino acid substitution p.Glu455Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.066% of alleles in individuals of African descent in gnomAD. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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