ClinVar Miner

Submissions for variant NM_000153.4(GALC):c.266C>T (p.Pro89Leu) (rs201422931)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000522459 SCV000618462 pathogenic not provided 2017-11-01 criteria provided, single submitter clinical testing The P89L variant in the GALC gene has been reported previously in several infants with low GALC activity on newborn screening, including at least one individual who was found to have a partial gene deletion on the oppositive GALC allele (in trans) (Orsini et al., 2016). The P89L variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The P89L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. Functional studies demonstrate that the P89L variant is associated with decreased enzyme activity (Saavedra-Matiz et al., 2016). We interpret P89L as a pathogenic variant.
Invitae RCV000673406 SCV000822850 uncertain significance Galactosylceramide beta-galactosidase deficiency 2018-04-13 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 89 of the GALC protein (p.Pro89Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs201422931, ExAC 0.02%). This variant has been observed on the opposite chromosome (in trans) from a GALC pathogenic variant in an individual with low GALC enzyme activity (PMID: 26795590). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 449966). This variant is also known as p.P73L in the literature. Experimental studies have shown that this missense change impairs GALC enzyme activity (PMID: 27638593). 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.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000522459 SCV000857362 uncertain significance not provided 2017-10-05 criteria provided, single submitter clinical testing
Counsyl RCV000673406 SCV000798605 uncertain significance Galactosylceramide beta-galactosidase deficiency 2018-03-14 no assertion criteria provided clinical testing

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