ClinVar Miner

Submissions for variant NM_052845.4(MMAB):c.197-1G>T (rs763935916)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000203326 SCV000797038 pathogenic Methylmalonic aciduria cblB type 2018-01-09 criteria provided, single submitter clinical testing
Foundation for Research in Genetics and Endocrinology,Institute of Human Genetics RCV000203326 SCV000579473 pathogenic Methylmalonic aciduria cblB type no assertion criteria provided clinical testing The observed variant is not reported in 1000 genomes database and is likely to be pathogenic by In Silico analysis using mutation taster.
GeneReviews RCV000203326 SCV000258532 pathogenic Methylmalonic aciduria cblB type 2016-01-07 no assertion criteria provided literature only
Integrated Genetics/Laboratory Corporation of America RCV000590462 SCV000699779 pathogenic Methylmalonic acidemia 2016-07-08 criteria provided, single submitter clinical testing Variant summary: The c.197-1G>T in MMAB gene is a splice-site variant that alters a highly conserved nucleotide with 5/5 in silico tools via Alamut predicting this variant to disrupt a canonical acceptor sequence. These predictions were confirmed by functional assay (Dobson, 2002). The variant is present in the large, broad control population, ExAC with an allele frequency of 3/121374 (1/40458), which does not exceed the estimated maximum allele frequency for a pathogenic allele in this gene of 1/714 (0.0014). The variant was found in multiple affected individuals with an established diagnosis of methylmalonic aciduria. Fibroblast lines from homozygous carriers had decreased incorporation of label from [14C] propionate into cellular macromolecules and decreased synthesis of AdoCbl from exogenous [57Co]CNCb. Lastly, reputable databases/diagnostic centers classify the variant of interest as Pathogenic. Taken together, the variant has been classified as Pathogenic.

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