ClinVar Miner

Submissions for variant NM_000035.4(ALDOB):c.488C>T (p.Ala163Val) (rs202210810)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000420841 SCV000531611 likely pathogenic not provided 2016-09-06 criteria provided, single submitter clinical testing The A163V variant in the ALDOB gene has been reported previously as a heterozygous variant identified in a newborn as part of a population based study of ALDOB variant frequency (Santer et al., 2005); however A163V has not been identified in an individual with hereditary fructose intolerance. The A163V variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The A163V 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 where amino acids with similar properties to Alanine are tolerated across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. The A163V variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded.
Invitae RCV000548672 SCV000626481 uncertain significance Hereditary fructosuria 2017-06-21 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 163 of the ALDOB protein (p.Ala163Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs202210810, ExAC 0.06%). This variant has not been reported in the literature in individuals with a ALDOB-related disease. ClinVar contains an entry for this variant (Variation ID: 389159). 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, this variant has uncertain impact on ALDOB function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000420841 SCV000707930 uncertain significance not provided 2018-06-21 criteria provided, single submitter clinical testing

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