Submissions for variant NM_017777.4(MKS1):c.1480C>T (p.Gln494Ter)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Myriad Genetics, Inc.	RCV002309374	SCV002603185	likely pathogenic	Bardet-Biedl syndrome 13; Meckel syndrome, type 1; Joubert syndrome 28	2022-03-31	criteria provided, single submitter	clinical testing	NM_017777.3(MKS1):c.1480C>T(Q494*) is expected to be pathogenic in the context of MKS1-related disorders. This variant is predicted to lead to an abnormal or absent protein product due to the creation of a premature termination codon in MKS1, a gene where loss-of-function variants are known to be pathogenic. Please note: this variant was assessed in the context of healthy population screening.
Invitae	RCV003099156	SCV003229560	pathogenic	Familial aplasia of the vermis; Meckel-Gruber syndrome	2022-10-31	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with MKS1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln494*) 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).
3billion	RCV003152794	SCV003841739	likely pathogenic	Meckel syndrome, type 1	2023-02-23	criteria provided, single submitter	clinical testing	The variant is not observed in the gnomAD v2.1.1 dataset. This variant was predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline.