ClinVar Miner

Submissions for variant NM_001360016.2(G6PD):c.383T>C (p.Leu128Pro) (rs78365220)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000178824 SCV000230986 pathogenic not provided 2013-10-29 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000778895 SCV000915300 pathogenic Glucose 6 phosphate dehydrogenase deficiency 2018-09-20 criteria provided, single submitter clinical testing The G6PD c.383T>C (p.Leu128Pro) variant has been reported in five studies and is found in a total of at least 27 patients (Ganczakowski et al. 1995, Hamel et al. 2002, Ainoon et al. 2003, Matsuoka et al. 2003, Hung et al. 2008). Control data are unavailable for p.Leu128Pro, which is reported at a frequency of 0.000052 in the South Asain population of the Genome Aggregation Database but this is based on one allele in a region of good sequence coverage so the variant is presumed to be rare. Gomez-Manzo et al. (2016) transformed the p.Leu128Pro variant into competent E. Coli which demonstrated low purification yield, low catalytic efficiency, low affinity for substrate, decrease in thermal stability, and low conformational stability compared with wild type (WT). Based on this evidence the p.Leu128Pro variant is interpreted as pathogenic for G6PD deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000799977 SCV000939671 pathogenic Anemia, nonspherocytic hemolytic, due to G6PD deficiency 2019-10-23 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 128 of the G6PD protein (p.Leu128Pro). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been observed in multiple individuals affected with G6PD deficiency (PMID: 7825590, 12215013, 11499668, 12497642, 21302115). ClinVar contains an entry for this variant (Variation ID: 93499). This variant has been reported to affect G6PD protein function (PMID: 27213370). For these reasons, this variant has been classified as Pathogenic.

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