ClinVar Miner

Submissions for variant NM_184041.4(ALDOA):c.760G>A (p.Val254Ile) (rs142759891)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000523742 SCV000618872 uncertain significance not specified 2017-07-18 criteria provided, single submitter clinical testing The V254I variant in the ALDOA gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The V254I variant is observed in 11/16490 (0.07%) alleles from individuals of South Asian background and in 13/66398 (0.02%) alleles from individuals of non-Finnish European background, in the ExAC dataset (Lek et al., 2016). The V254I variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret V254I as a variant of uncertain significance.
Invitae RCV000696203 SCV000824755 uncertain significance HNSHA due to aldolase A deficiency 2018-05-03 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 254 of the ALDOA protein (p.Val254Ile). The valine residue is highly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs142759891, ExAC 0.07%). This variant has not been reported in the literature in individuals with ALDOA-related disease. ClinVar contains an entry for this variant (Variation ID: 450306). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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