ClinVar Miner

Submissions for variant NM_172250.3(MMAA):c.833G>A (p.Gly278Asp) (rs761964238)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000667825 SCV000792330 uncertain significance Vitamin B12-responsive methylmalonic acidemia type cblA 2017-06-14 criteria provided, single submitter clinical testing
Invitae RCV000667825 SCV001373260 uncertain significance Vitamin B12-responsive methylmalonic acidemia type cblA 2019-10-10 criteria provided, single submitter clinical testing This sequence change replaces glycine with aspartic acid at codon 278 of the MMAA protein (p.Gly278Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. This variant is present in population databases (rs761964238, ExAC 0.006%). This variant has been observed in individuals affected with MMACblA (PMID: 23716945, Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 552542). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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