Submissions for variant NM_017777.4(MKS1):c.1126dup (p.Thr376fs)

dbSNP: rs2143753386

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Pathology and Clinical Laboratory Medicine, King Fahad Medical City	RCV001824178	SCV002073804	likely pathogenic	Meckel syndrome, type 1		criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001882748	SCV002242965	pathogenic	Familial aplasia of the vermis; Meckel-Gruber syndrome	2023-12-09	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Thr376Asnfs*3) in the MKS1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MKS1 are known to be pathogenic (PMID: 19466712, 24886560, 26490104). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Meckel–Gruber syndrome (PMID: 23169490). ClinVar contains an entry for this variant (Variation ID: 1252059). 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.
Revvity Omics, Revvity	RCV003146224	SCV003830961	likely pathogenic	not provided	2022-01-10	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV001824178	SCV001870498	pathogenic	Meckel syndrome, type 1	2021-04-29	no assertion criteria provided	research