ClinVar Miner

Submissions for variant NM_030665.4(RAI1):c.1471G>A (p.Glu491Lys)

gnomAD frequency: 0.00001  dbSNP: rs527757515
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000499820 SCV000596705 uncertain significance not specified 2015-11-19 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000765336 SCV000896599 uncertain significance Smith-Magenis syndrome 2018-10-31 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002524278 SCV003516717 uncertain significance not provided 2023-10-29 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 491 of the RAI1 protein (p.Glu491Lys). This variant is present in population databases (rs527757515, gnomAD 0.007%). This missense change has been observed in individual(s) with neurodevelopmental disorders (PMID: 28135719). This variant is also known as g.17697733. ClinVar contains an entry for this variant (Variation ID: 436495). 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 RAI1 protein function with a positive predictive value of 80%. 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.
CeGaT Center for Human Genetics Tuebingen RCV002524278 SCV004142343 uncertain significance not provided 2023-08-01 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004742461 SCV005352877 uncertain significance RAI1-related disorder 2024-09-16 no assertion criteria provided clinical testing The RAI1 c.1471G>A variant is predicted to result in the amino acid substitution p.Glu491Lys. This variant was reported to have occurred de novo in an individual with a developmental disorder (Supplementary Table 1, McRae et al 2017. PubMed ID: 28135719). This variant is reported in 0.0065% of alleles in individuals of South Asian descent in gnomAD. 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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