Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002776366 | SCV003034680 | uncertain significance | L-2-hydroxyglutaric aciduria | 2022-11-01 | criteria provided, single submitter | clinical testing | 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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. This variant has not been reported in the literature in individuals affected with L2HGDH-related conditions. 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 sequence change falls in intron 1 of the L2HGDH gene. It does not directly change the encoded amino acid sequence of the L2HGDH protein. It affects a nucleotide within the consensus splice site. |
Ambry Genetics | RCV002790761 | SCV003554863 | uncertain significance | Inborn genetic diseases | 2021-10-21 | criteria provided, single submitter | clinical testing | The c.140+3G>C intronic alteration consists of a G to C substitution 3 nucleotides after exon 1 of the L2HGDH gene. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |