ClinVar Miner

Submissions for variant NM_052845.4(MMAB):c.377C>T (p.Ser126Leu) (rs771053425)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000673685 SCV000798915 uncertain significance Methylmalonic aciduria cblB type 2018-03-28 criteria provided, single submitter clinical testing
GeneDx RCV000498258 SCV000589819 likely pathogenic not provided 2016-04-12 criteria provided, single submitter clinical testing The S126L variant has not been published in association with methylmalonic acidaemia, cblB type, nor has it been reported as a benign variant to our knowledge. Functional analysis of S126L found that it is associated with impaired ATP and cobalamin binding resulting in significantly reduced enzyme activity compared to wild type (Fan et al., 2008). The S126L variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is not conserved. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.

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