ClinVar Miner

Submissions for variant NM_001165927.1(MKS1):c.994+1G>A (rs199874059)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000668139 SCV000792690 likely pathogenic Bardet-Biedl syndrome 13; Meckel syndrome type 1; Joubert syndrome 28 2017-07-07 criteria provided, single submitter clinical testing
Invitae RCV001038005 SCV001201446 pathogenic Joubert syndrome; Meckel-Gruber syndrome 2020-08-20 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 11 of the MKS1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs199874059, ExAC 0.009%). This variant has been observed in combination with another MKS1 variant in an individual affected with Meckel-Gruber syndrome (PMID: 17377820). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as IVS11+1G>A in the literature. ClinVar contains an entry for this variant (Variation ID: 1391) Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MKS1 are known to be pathogenic (PMID: 17397051). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000022414 SCV000043099 pathogenic Meckel syndrome type 1 2007-06-01 no assertion criteria provided literature only
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) RCV000022414 SCV000082434 probable-pathogenic Meckel syndrome type 1 no assertion criteria provided not provided Converted during submission to Likely pathogenic.

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