ClinVar Miner

Submissions for variant NM_000153.4(GALC):c.349A>G (p.Met117Val) (rs145580093)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000078201 SCV000110039 uncertain significance not provided 2016-08-26 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000078201 SCV000280686 pathogenic not provided 2015-11-11 criteria provided, single submitter clinical testing
Invitae RCV000545705 SCV000627132 uncertain significance Galactosylceramide beta-galactosidase deficiency 2017-06-09 criteria provided, single submitter clinical testing This sequence change replaces methionine with valine at codon 117 of the GALC protein (p.Met117Val). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and valine. This variant is present in population databases (rs145580093, ExAC 0.1%). This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual affected with Krabbe disease (PMID: 23430802). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. It has also been reported in multiple infants with low GALC enzyme activity who had been referred for confirmatory testing of abnormal newborn screening results. However, the other variant was not specified in the publication (PMID: 26795590). ClinVar contains an entry for this variant (Variation ID: 92504). This variant has been observed in an individual with GALC enzyme activity less than 10% of normal controls, findings that are highly specific for Krabbe disease (PMID: 23430802). In summary, this variant has uncertain impact on GALC function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Counsyl RCV000545705 SCV000800651 uncertain significance Galactosylceramide beta-galactosidase deficiency 2018-01-09 criteria provided, single submitter clinical testing

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