Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002711109 | SCV003001215 | uncertain significance | not provided | 2022-05-10 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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: "Benign"; Align-GVGD: "Class C55"). This variant has not been reported in the literature in individuals affected with CHD4-related conditions. This variant is present in population databases (rs777539073, gnomAD 0.0009%). This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 709 of the CHD4 protein (p.Thr709Ala). |
Prevention |
RCV003395503 | SCV004121390 | uncertain significance | CHD4-related disorder | 2022-12-19 | criteria provided, single submitter | clinical testing | The CHD4 c.2125A>G variant is predicted to result in the amino acid substitution p.Thr709Ala. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.00089% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/12-6703813-T-C). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |