ClinVar Miner

Submissions for variant NM_170784.3(MKKS):c.1625T>G (p.Leu542Trp)

gnomAD frequency: 0.00014  dbSNP: rs372944937
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Genetics RCV001332286 SCV001524546 uncertain significance Bardet-Biedl syndrome 6 2019-03-15 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Labcorp Genetics (formerly Invitae), Labcorp RCV001367708 SCV001564068 uncertain significance Bardet-Biedl syndrome; McKusick-Kaufman syndrome 2022-10-17 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with tryptophan, which is neutral and slightly polar, at codon 542 of the MKKS protein (p.Leu542Trp). This variant is present in population databases (rs372944937, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with MKKS-related conditions. ClinVar contains an entry for this variant (Variation ID: 1030676). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MKKS 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.
GeneDx RCV001773667 SCV002002391 uncertain significance not provided 2021-02-17 criteria provided, single submitter clinical testing 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
Ambry Genetics RCV004960793 SCV005445157 uncertain significance Inborn genetic diseases 2024-08-01 criteria provided, single submitter clinical testing The c.1625T>G (p.L542W) alteration is located in exon 6 (coding exon 4) of the MKKS gene. This alteration results from a T to G substitution at nucleotide position 1625, causing the leucine (L) at amino acid position 542 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV005023057 SCV005663352 uncertain significance McKusick-Kaufman syndrome; Bardet-Biedl syndrome 6 2024-05-24 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004531117 SCV004718657 uncertain significance MKKS-related disorder 2024-01-03 no assertion criteria provided clinical testing The MKKS c.1625T>G variant is predicted to result in the amino acid substitution p.Leu542Trp. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.032% of alleles in individuals of African descent in gnomAD. 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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