Submissions for variant NM_001134407.3(GRIN2A):c.4021dup (p.Ser1341fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV003154513	SCV003842830	likely pathogenic	not provided	2022-09-16	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation, as the last 124 amino acids are replaced with 24 different amino acids, and other loss-of-function variants have been reported downstream in HGMD; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp	RCV005100926	SCV005729601	pathogenic	Landau-Kleffner syndrome	2024-11-16	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ser1341Lysfs*25) in the GRIN2A gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 124 amino acid(s) of the GRIN2A protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with GRIN2A-related conditions. ClinVar contains an entry for this variant (Variation ID: 2444780). This variant disrupts a region of the GRIN2A protein in which other variant(s) (p.Asn1397Glnfs*23) have been determined to be pathogenic (PMID: 25724810). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.