ClinVar Miner

Submissions for variant NM_052845.4(MMAB):c.577G>A (p.Glu193Lys)

gnomAD frequency: 0.00001  dbSNP: rs749758687
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000669558 SCV000794321 uncertain significance Methylmalonic aciduria, cblB type 2017-09-22 criteria provided, single submitter clinical testing
Invitae RCV000669558 SCV001221775 pathogenic Methylmalonic aciduria, cblB type 2023-10-31 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 193 of the MMAB protein (p.Glu193Lys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with methylmalonic aciduria (PMID: 12471062, 25760844, 31622506, 33453710, 34796408). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 554009). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MMAB protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects MMAB function (PMID: 16439175, 34757128). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000669558 SCV004193134 likely pathogenic Methylmalonic aciduria, cblB type 2023-10-16 criteria provided, single submitter clinical testing
Baumgartner lab, University Children's Hospital Zurich RCV000669558 SCV001738803 pathogenic Methylmalonic aciduria, cblB type 2021-06-01 no assertion criteria provided clinical testing

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