ClinVar Miner

Submissions for variant NM_007327.4(GRIN1):c.1923G>A (p.Met641Ile) (rs1060500046)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GenomeConnect, ClinGen RCV000844969 SCV000986794 not provided GRIN1-Related Disorder no assertion provided phenotyping only Variant interpretted as pathogenic and reported on 05/15/2018 by GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Invitae RCV000473483 SCV000541368 pathogenic Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant 2016-08-10 criteria provided, single submitter clinical testing This sequence change replaces methionine with isoleucine at codon 641 of the GRIN1 protein (p.Met641Ile). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has been shown to arise de novo in an individual affected with severe intellectual disability, movement disorder, and seizures (PMID: 27164704). It has also been reported to arise de novo in an individual affected with early onset epileptic encephalopathy (PMID: 25864721). However, mosaicism was reported in that individual, and this p.Met641Ile variant represented only 13.4-19.7% of the alleles. Family studies indicate this missense variant likely was not inherited from either parent (i.e. occurred de novo) in an individual with disease (Invitae database). For these reasons, this variant has been classified as Pathogenic.

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