Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002922769 | SCV003263271 | uncertain significance | 3-methylcrotonyl-CoA carboxylase 1 deficiency | 2021-08-31 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with leucine at codon 548 of the MCCC1 protein (p.Ser548Leu). The serine residue is moderately conserved and there is a large physicochemical difference between serine and leucine. This variant is present in population databases (rs754187797, ExAC 0.009%). This variant has not been reported in the literature in individuals affected with MCCC1-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. |
Prevention |
RCV003418651 | SCV004108482 | uncertain significance | MCCC1-related disorder | 2023-01-10 | criteria provided, single submitter | clinical testing | The MCCC1 c.1643C>T variant is predicted to result in the amino acid substitution p.Ser548Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0080% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/3-182751817-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |