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
Invitae RCV000473483 SCV000541368 pathogenic Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant 2020-02-11 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 observed to be de novo in individuals affected with early onset epileptic encephalopathy (PMID: 27164704, Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). This variant disrupts the p.Met641 amino acid residue in GRIN1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 30355546, Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
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.

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