ClinVar Miner

Submissions for variant NM_001170629.2(CHD8):c.5372G>A (p.Arg1791Gln)

gnomAD frequency: 0.00001  dbSNP: rs370298280
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002316048 SCV000847474 uncertain significance Inborn genetic diseases 2016-08-05 criteria provided, single submitter clinical testing The p.R1791Q variant (also known as c.5372G>A), located in coding exon 29 of the CHD8 gene, results from a G to A substitution at nucleotide position 5372. The arginine at codon 1791 is replaced by glutamine, an amino acid with highly similar properties. This variant was previously reported in the SNPDatabase as rs370298280. Based on data from the NHLBI Exome Sequencing Project (ESP), the A allele has an overall frequency of approximately 0.01% (1/12042) total alleles studied, having been observed in 0.03% (1/3796) African American alleles. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001868344 SCV002260141 uncertain significance not provided 2024-05-22 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1791 of the CHD8 protein (p.Arg1791Gln). This variant is present in population databases (rs370298280, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with CHD8-related conditions. ClinVar contains an entry for this variant (Variation ID: 588128). 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 CHD8 protein function with a negative 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.
Fulgent Genetics, Fulgent Genetics RCV002485802 SCV002790270 uncertain significance Intellectual developmental disorder with autism and macrocephaly 2022-01-06 criteria provided, single submitter clinical testing

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