ClinVar Miner

Submissions for variant NM_017777.4(MKS1):c.1095G>C (p.Met365Ile)

gnomAD frequency: 0.00002  dbSNP: rs1440032995
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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 RCV001912081 SCV002139894 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome 2023-10-03 criteria provided, single submitter clinical testing This sequence change affects codon 365 of the MKS1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the MKS1 protein. This variant also falls at the last nucleotide of exon 12, which is part of the consensus splice site for this exon. This variant is not present in population databases (gnomAD no frequency). 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: 1376687). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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 RCV005016719 SCV005647334 uncertain significance Bardet-Biedl syndrome 13; Meckel syndrome, type 1; Joubert syndrome 28 2024-01-10 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004733395 SCV005356782 uncertain significance MKS1-related disorder 2024-03-07 no assertion criteria provided clinical testing The MKS1 c.1095G>C variant is predicted to result in the amino acid substitution p.Met365Ile. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. 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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