ClinVar Miner

Submissions for variant NM_017777.4(MKS1):c.958G>A (p.Val320Ile)

gnomAD frequency: 0.00002  dbSNP: rs386834053
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000735097 SCV000863292 uncertain significance not provided 2018-09-06 criteria provided, single submitter clinical testing
Diagnostics Division, CENTRE FOR DNA FINGERPRINTING AND DIAGNOSTICS RCV000735871 SCV000864077 likely pathogenic Leber congenital amaurosis 6; Meckel syndrome, type 1 2018-01-01 criteria provided, single submitter research The individual also harbours an earlier reported variant SCV000323252.1 by us, responsible for OMIM phenotype condition 613826.
Invitae RCV001853066 SCV002268178 pathogenic Familial aplasia of the vermis; Meckel-Gruber syndrome 2023-12-02 criteria provided, single submitter clinical testing This sequence change affects codon 320 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 10, which is part of the consensus splice site for this exon. This variant is present in population databases (rs386834053, gnomAD 0.005%). This variant has been observed in individual(s) with MKS1-related conditions (PMID: 17397051, 31191208, 35587316). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 56627). 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. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV003474638 SCV004194931 likely pathogenic Bardet-Biedl syndrome 13 2023-08-29 criteria provided, single submitter clinical testing
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) RCV000050040 SCV000082449 probable-pathogenic Meckel syndrome, type 1 no assertion criteria provided not provided Converted during submission to Likely pathogenic.

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