ClinVar Miner

Submissions for variant NM_170784.3(MKKS):c.697A>C (p.Ile233Leu)

gnomAD frequency: 0.00016  dbSNP: rs141201812
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000638613 SCV000760150 uncertain significance Bardet-Biedl syndrome; McKusick-Kaufman syndrome 2022-10-17 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 233 of the MKKS protein (p.Ile233Leu). This variant is present in population databases (rs141201812, gnomAD 0.05%). 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: 532031). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 RCV003162854 SCV003865811 uncertain significance Inborn genetic diseases 2023-02-23 criteria provided, single submitter clinical testing The c.697A>C (p.I233L) alteration is located in exon 3 (coding exon 1) of the MKKS gene. This alteration results from a A to C substitution at nucleotide position 697, causing the isoleucine (I) at amino acid position 233 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx RCV004797848 SCV005419593 uncertain significance not provided 2024-05-29 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
Fulgent Genetics, Fulgent Genetics RCV005027751 SCV005663395 uncertain significance McKusick-Kaufman syndrome; Bardet-Biedl syndrome 6 2024-04-17 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004527698 SCV004105852 uncertain significance MKKS-related disorder 2024-07-24 no assertion criteria provided clinical testing The MKKS c.697A>C variant is predicted to result in the amino acid substitution p.Ile233Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.054% of alleles in individuals of Latino descent in gnomAD, which may be too common to be a primary cause of disease. 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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