ClinVar Miner

Submissions for variant NM_030665.4(RAI1):c.1882G>A (p.Glu628Lys)

gnomAD frequency: 0.00006  dbSNP: rs371291565
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002007636 SCV002266412 uncertain significance not provided 2023-10-07 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 628 of the RAI1 protein (p.Glu628Lys). This variant is present in population databases (rs371291565, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with RAI1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1474485). 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 not expected to disrupt RAI1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Genetics and Molecular Pathology, SA Pathology RCV002272552 SCV002556876 likely benign Smith-Magenis syndrome 2020-11-19 criteria provided, single submitter clinical testing The RAI1 c.1882G>A variant is a single nucleotide change from guanine to adenine at codon 1882 which is predicted to change the amino acid glutamic acid at position 628 in the protein to lysine. The variant is in exon 3 of 6. The variant has been reported in dbSNP (rs371291565) and is rare in population databases (gnomAD 14/281,448 alleles, frequency in Europeans 0.01%, 0 homozygotes). This variant has not been reported in the ClinVar or HGMD disease databases. Computational predictions are mixed (neither PP3 nor BP4 applied).
Ambry Genetics RCV002573407 SCV003751160 likely benign Inborn genetic diseases 2022-09-22 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
PreventionGenetics, part of Exact Sciences RCV004744191 SCV005352261 uncertain significance RAI1-related disorder 2024-04-05 no assertion criteria provided clinical testing The RAI1 c.1882G>A variant is predicted to result in the amino acid substitution p.Glu628Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.011% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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