Submissions for variant NM_152594.3(SPRED1):c.796_797del (p.Met266fs)

dbSNP: rs864622410

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000204318	SCV000260510	pathogenic	Legius syndrome	2023-02-09	criteria provided, single submitter	clinical testing	This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Met266Valfs*4) in the SPRED1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 179 amino acid(s) of the SPRED1 protein. This premature translational stop signal has been observed in individuals with cafe au lait macules (PMID: 17704776; Invitae). ClinVar contains an entry for this variant (Variation ID: 220172). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this premature translational stop signal affects SPRED1 function (PMID: 17704776, 22751498). For these reasons, this variant has been classified as Pathogenic.
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000204318	SCV000782325	pathogenic	Legius syndrome	2016-11-01	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001813427	SCV002060442	pathogenic	Noonan syndrome and Noonan-related syndrome	2020-02-01	criteria provided, single submitter	clinical testing
MGZ Medical Genetics Center	RCV000204318	SCV002581091	likely pathogenic	Legius syndrome	2022-07-27	criteria provided, single submitter	clinical testing