ClinVar Miner

Submissions for variant NM_002860.4(ALDH18A1):c.1351G>A (p.Val451Met)

gnomAD frequency: 0.00004  dbSNP: rs111344269
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV000761742 SCV000891927 uncertain significance not provided 2024-06-01 criteria provided, single submitter clinical testing
New York Genome Center RCV001836877 SCV002097950 uncertain significance Cutis laxa, autosomal dominant 3 2021-02-19 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003768293 SCV002135508 uncertain significance Cutis laxa, autosomal dominant 3; Autosomal dominant spastic paraplegia type 9; de Barsy syndrome 2024-09-30 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 451 of the ALDH18A1 protein (p.Val451Met). This variant is present in population databases (rs111344269, gnomAD 0.008%). This missense change has been observed in individual(s) with ALDH18A1-related conditions (PMID: 37712079). ClinVar contains an entry for this variant (Variation ID: 623751). 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) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ALDH18A1 protein function. 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.
Revvity Omics, Revvity RCV000761742 SCV003823123 uncertain significance not provided 2019-12-19 criteria provided, single submitter clinical testing
Neurogenomics Lab, Neuroscience Institute, University Of Cape Town RCV003320368 SCV003930351 uncertain significance Autosomal recessive complex spastic paraplegia type 9B 2024-05-22 criteria provided, single submitter research PM2_supporting: The highest population allele frequency in gnomAD v4.0 is 0.00007811 (0.008%; 5/64012 alleles in European Finnish population). This variant is absent from gnomAD v2.1.1 (adequate coverage >20x confirmed) and an internal database of 1074 control alleles. PM1 met: variant occurs in the G5PR functional domain together with other recessive pathogenic variants.
GeneDx RCV000761742 SCV005383541 uncertain significance not provided 2024-02-15 criteria provided, single submitter clinical testing Identified in apparently homozygous state in a patient with hereditary spastic paraplegia (HSP) (PMID: 37712079); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 37712079)

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