ClinVar Miner

Submissions for variant NM_016222.4(DDX41):c.809C>T (p.Ala270Val)

gnomAD frequency: 0.00001  dbSNP: rs745544108
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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 RCV002598260 SCV002955087 uncertain significance not provided 2024-07-21 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 270 of the DDX41 protein (p.Ala270Val). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with myeloid neoplasm (PMID: 36322930, 36455200). ClinVar contains an entry for this variant (Variation ID: 1917434). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
Baylor Genetics RCV004571186 SCV005059407 uncertain significance DDX41-related hematologic malignancy predisposition syndrome 2023-12-19 criteria provided, single submitter clinical testing
GeneDx RCV002598260 SCV005375629 likely pathogenic not provided 2023-11-27 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27721487, 36455200, 36923434, 37506341, 36322930, RoubinetM2023[article])
Ambry Genetics RCV005321183 SCV005990068 uncertain significance Inborn genetic diseases 2025-02-28 criteria provided, single submitter clinical testing The p.A270V variant (also known as c.809C>T), located in coding exon 9 of the DDX41 gene, results from a C to T substitution at nucleotide position 809. The alanine at codon 270 is replaced by valine, an amino acid with similar properties. This variant was reported as germline in a patient with myelodysplastic syndrome at age 82 (Makishima H et al. Blood, 2023 Feb;141:534-549). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.

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