ClinVar Miner

Submissions for variant NM_022552.5(DNMT3A):c.1706C>T (p.Pro569Leu)

gnomAD frequency: 0.00002  dbSNP: rs772310511
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001060402 SCV001225085 uncertain significance Tatton-Brown-Rahman overgrowth syndrome 2024-09-14 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 569 of the DNMT3A protein (p.Pro569Leu). This variant is present in population databases (rs772310511, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with DNMT3A-related conditions. ClinVar contains an entry for this variant (Variation ID: 855198). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt DNMT3A 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.
GeneDx RCV001776115 SCV002012902 uncertain significance not provided 2019-06-04 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
PreventionGenetics, part of Exact Sciences RCV004746225 SCV005361361 uncertain significance DNMT3A-related disorder 2024-08-28 no assertion criteria provided clinical testing The DNMT3A c.1706C>T variant is predicted to result in the amino acid substitution p.Pro569Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0089% of alleles in individuals of Latino 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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