Submissions for variant NM_006772.3(SYNGAP1):c.1393del (p.Leu465fs)

dbSNP: rs1057518183

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000413721	SCV000491624	pathogenic	not provided	2018-06-04	criteria provided, single submitter	clinical testing	The c.1393delC pathogenic variant in the SYNGAP1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.1393delC variant causes a frameshift starting with codon Leucine 465, changes this amino acid to a Phenylalanine residue, and creates a premature Stop codon at position 9 of the new reading frame, denoted p.Leu465PhefsX9. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.1393delC variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.1393delC as a pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003615837	SCV004551593	pathogenic	Intellectual disability, autosomal dominant 5	2023-12-25	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Leu465Phefs*9) in the SYNGAP1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SYNGAP1 are known to be pathogenic (PMID: 23161826, 23708187, 26989088). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with SYNGAP1-related conditions (PMID: 30541864). ClinVar contains an entry for this variant (Variation ID: 373062). For these reasons, this variant has been classified as Pathogenic.