ClinVar Miner

Submissions for variant NM_000157.4(GBA):c.1223C>T (p.Thr408Met) (rs75548401)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000244995 SCV000111205 benign not specified 2016-05-09 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000079335 SCV000281415 likely benign not provided 2015-12-23 criteria provided, single submitter clinical testing Converted during submission to Likely benign.
PreventionGenetics,PreventionGenetics RCV000244995 SCV000305637 benign not specified criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000079335 SCV000780298 likely benign not provided 2020-03-01 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000244995 SCV000919416 benign not specified 2018-01-02 criteria provided, single submitter clinical testing Variant summary: The GBA c.1223C>T (p.Thr408Met, also known as Thr369Met) variant located in the glycosyl hydrolase family 30, TIM-barrel domain (via InterPro) involves the alteration of a non-conserved nucleotide and 2/3 in silico tools predict a benign outcome for this variant (SNPsandGO and MutationTaster not captured due to low reliability index and p-value). This variant was found in 1708/277314 (7 homozygotes) control chromosomes (gnomAD and publication controls) at a frequency of 0.0061591, which is approximately 1 times the estimated maximal expected allele frequency of a pathogenic GBA variant (0.005), suggesting this variant is likely a benign polymorphism. Multiple publications have cited the variant in affected individuals including a co-occurrence with another pathogenic GBA variant, D409H (also known as D448H - scored DV)(Hodanova_1999). Another publication, Walker_2003, cites the variant, T369M, as a polymorphism. A publication, Hodanova_2003, does indicate the variant could cause a functional impact but the authors state that at most would be a mild mutation even on the verge of a polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as "likely benign/benign." Taken together, this variant is classified as benign.
DST/NWU Preclinical Drug Development Platform,North-West University RCV000416597 SCV000245439 uncertain significance Parkinson disease, late-onset 2015-09-08 no assertion criteria provided research
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000079335 SCV000800926 benign not provided 2017-05-17 no assertion criteria provided clinical testing

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