Submissions for variant NM_017777.4(MKS1):c.1115_1117del (p.Ser372del)

dbSNP: rs754279998

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
UW Hindbrain Malformation Research Program, University of Washington	RCV000201670	SCV000256447	pathogenic	Familial aplasia of the vermis	2015-02-23	criteria provided, single submitter	research
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV000414929	SCV000492770	pathogenic	Polydactyly; Global developmental delay; Rotary nystagmus; Limb undergrowth; Chronic kidney disease	2015-10-23	criteria provided, single submitter	clinical testing
Counsyl	RCV000665372	SCV000789485	likely pathogenic	Bardet-Biedl syndrome 13; Meckel syndrome, type 1; Joubert syndrome 28	2017-02-03	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000691391	SCV000819167	pathogenic	Familial aplasia of the vermis; Meckel-Gruber syndrome	2023-12-21	criteria provided, single submitter	clinical testing	This variant, c.1115_1117del, results in the deletion of 1 amino acid(s) of the MKS1 protein (p.Ser372del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs754279998, gnomAD 0.003%). This variant has been observed in individual(s) with Joubert syndrome (PMID: 24886560, 26092869, 27570071). This variant is also known as c.1085_1088delCCT (p.S362del). ClinVar contains an entry for this variant (Variation ID: 217677). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. For these reasons, this variant has been classified as Pathogenic.
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV001197092	SCV001367728	pathogenic	Bardet-Biedl syndrome 13	2016-01-01	criteria provided, single submitter	clinical testing	This variant was classified as: Pathogenic. This variant was detected in homozygous state.
Baylor Genetics	RCV001197092	SCV004194928	pathogenic	Bardet-Biedl syndrome 13	2023-12-27	criteria provided, single submitter	clinical testing
Laboratory of Medical Genetics, National & Kapodistrian University of Athens	RCV001272923	SCV005051861	likely pathogenic	Meckel syndrome, type 1	2024-02-01	criteria provided, single submitter	curation
OMIM	RCV000241545	SCV000301466	pathogenic	Joubert syndrome 28	2016-09-23	no assertion criteria provided	literature only
Natera, Inc.	RCV001272923	SCV001455370	pathogenic	Meckel syndrome, type 1	2020-09-16	no assertion criteria provided	clinical testing
Gene Discovery Core-Manton Center, Boston Children's Hospital	RCV000241545	SCV001768735	pathogenic	Joubert syndrome 28	2020-02-14	no assertion criteria provided	research	This variant is interpreted as Pathogenic for Joubert syndrome; Autosomal Recessive. PM1- Located in a mutational hot spot and/or critical and well-established functional domain (e.g., active site of an enzyme) without benign variation. PM2- Absent from controls or at extremely low frequency if recessive (0 homozygotes in gnomad). PM4- Protein length changes as a result of in-frame deletions/insertions in a non-repeat region or stop-loss variants. PP3- Multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc.). PP5: Reputable source recently reports variant as pathogenic, but the evidence is not available to the laboratory to perform an independent evaluation, 6 nonconflicting ClinVar entries, (PMIDs: 24886560, 26092869, 26490104 and 27570071).
GeneReviews	RCV000241545	SCV001792275	not provided	Joubert syndrome 28		no assertion provided	literature only