Submissions for variant NM_000834.5(GRIN2B):c.1547A>G (p.Asn516Ser)

dbSNP: rs886041295

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000317346	SCV000329650	pathogenic	not provided	2023-10-02	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 32144935, 28377535, 31526516, 27839871)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000655320	SCV000777250	pathogenic	Intellectual disability, autosomal dominant 6; Developmental and epileptic encephalopathy, 27	2023-09-05	criteria provided, single submitter	clinical testing	This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt GRIN2B protein function. ClinVar contains an entry for this variant (Variation ID: 279975). This missense change has been observed in individual(s) with clinical features of GRIN2B-related condition (PMID: 28377535). In at least one individual the variant was observed to be de novo. This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 516 of the GRIN2B protein (p.Asn516Ser).
Institute of Human Genetics, University of Leipzig Medical Center	RCV001172351	SCV001335400	likely pathogenic	Intellectual disability, autosomal dominant 6	2017-04-04	criteria provided, single submitter	clinical testing	This variant was identified as de novo (maternity and paternity confirmed).
Institute of Human Genetics, University of Leipzig Medical Center	RCV001723869	SCV001950101	pathogenic	Developmental and epileptic encephalopathy, 27	2022-01-12	criteria provided, single submitter	clinical testing	This variant was identified as de novo (maternity and paternity confirmed)._x000D_ Criteria applied: PS2_VSTR, PS4_MOD, PM2_SUP, PP3
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV001172351	SCV002759392	likely pathogenic	Intellectual disability, autosomal dominant 6	2022-12-08	criteria provided, single submitter	clinical testing
GenomeConnect - Simons Searchlight	RCV001265472	SCV001443609	pathogenic	Complex neurodevelopmental disorder	2018-01-12	no assertion criteria provided	provider interpretation	Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2018-01-12 and interpreted as Pathogenic. The reporting laboratory might also submit to ClinVar. This variant was identified in multiple probands enrolled in Simons Searchlight.