ClinVar Miner

Submissions for variant NM_024884.3(L2HGDH):c.1047G>A (p.Met349Ile)

gnomAD frequency: 0.00003  dbSNP: rs746089124
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001931797 SCV002209165 uncertain significance L-2-hydroxyglutaric aciduria 2021-12-02 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 349 of the L2HGDH protein (p.Met349Ile). This variant is present in population databases (rs746089124, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with L2HGDH-related conditions. 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. 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.
Ambry Genetics RCV002562103 SCV003718229 uncertain significance Inborn genetic diseases 2021-10-12 criteria provided, single submitter clinical testing The c.1047G>A (p.M349I) alteration is located in exon 8 (coding exon 8) of the L2HGDH gene. This alteration results from a G to A substitution at nucleotide position 1047, causing the methionine (M) at amino acid position 349 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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