Submissions for variant NM_017777.4(MKS1):c.1408-1dup

dbSNP: rs762668200

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000501226	SCV000595797	pathogenic	Meckel syndrome, type 1	2016-05-19	criteria provided, single submitter	clinical testing
Invitae	RCV000823733	SCV000964603	pathogenic	Familial aplasia of the vermis; Meckel-Gruber syndrome	2024-01-09	criteria provided, single submitter	clinical testing	This sequence change results in a frameshift in the MKS1 gene (p.Glu471Glyfs*120). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 89 amino acid(s) of the MKS1 protein and extend the protein by 30 additional amino acid residues. This variant is present in population databases (rs762668200, gnomAD 0.09%). 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: 435876). This variant results in an extension of the MKS1 protein. Other variant(s) that result in a similarly extended protein product (p.Thr485Argfs*107) have been determined to be pathogenic (PMID: 17185389, 17397051). This suggests that these extensions are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Medical Genetics Center, Maternal and Child Health Hospital of Hubei Province	RCV000501226	SCV003915600	likely pathogenic	Meckel syndrome, type 1	2021-03-19	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003476196	SCV004194921	likely pathogenic	Bardet-Biedl syndrome 13	2023-10-17	criteria provided, single submitter	clinical testing