ClinVar Miner

Submissions for variant NM_170784.3(MKKS):c.464G>A (p.Arg155His)

gnomAD frequency: 0.00003  dbSNP: rs138111422
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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 RCV001341949 SCV001535846 uncertain significance Bardet-Biedl syndrome; McKusick-Kaufman syndrome 2022-01-12 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 155 of the MKKS protein (p.Arg155His). This variant is present in population databases (rs138111422, gnomAD 0.003%). 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: 1038618). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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.
Fulgent Genetics, Fulgent Genetics RCV002493751 SCV002796955 uncertain significance McKusick-Kaufman syndrome; Bardet-Biedl syndrome 6 2022-03-30 criteria provided, single submitter clinical testing
New York Genome Center RCV002493751 SCV004046538 uncertain significance McKusick-Kaufman syndrome; Bardet-Biedl syndrome 6 2023-02-06 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004531132 SCV004115095 uncertain significance MKKS-related disorder 2023-10-05 criteria provided, single submitter clinical testing The MKKS c.464G>A variant is predicted to result in the amino acid substitution p.Arg155His. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0062% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/20-10393699-C-T). Of note, a different amino acid substitution affecting the same amino acid (p.Arg155Leu) has been reported in an individual with Bardet-Biedl syndrome; however, a second variant was not identified (Slavotinek et al. 2002. PubMed ID: 12107442). At this time, the clinical significance of this variant is uncertain.
Ambry Genetics RCV004035977 SCV004969973 uncertain significance Inborn genetic diseases 2022-01-26 criteria provided, single submitter clinical testing The c.464G>A (p.R155H) alteration is located in exon 3 (coding exon 1) of the MKKS gene. This alteration results from a G to A substitution at nucleotide position 464, causing the arginine (R) at amino acid position 155 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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