Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Center for Pediatric Genomic Medicine, |
RCV000438685 | SCV000511476 | uncertain significance | not provided | 2017-02-08 | criteria provided, single submitter | clinical testing | Converted during submission to Uncertain significance. |
Invitae | RCV001339627 | SCV001533383 | uncertain significance | Methylmalonic aciduria, cblA type | 2022-08-19 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 381 of the MMAA protein (p.Thr381Ile). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MMAA-related conditions. ClinVar contains an entry for this variant (Variation ID: 377200). 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 not expected to disrupt MMAA protein function. 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. |
Ambry Genetics | RCV002524729 | SCV003735069 | uncertain significance | Inborn genetic diseases | 2021-09-21 | criteria provided, single submitter | clinical testing | The c.1142C>T (p.T381I) alteration is located in exon 7 (coding exon 6) of the MMAA gene. This alteration results from a C to T substitution at nucleotide position 1142, causing the threonine (T) at amino acid position 381 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Illumina Laboratory Services, |
RCV000438685 | SCV003802832 | uncertain significance | not provided | 2022-09-23 | criteria provided, single submitter | clinical testing | The MMAA c.1142C>T (p.Thr381Ile) missense variant results in the substitution of threonine at amino acid position 381 with isoleucine. To our knowledge, this variant has not been reported in the peer-reviewed literature. This variant is not found in version 2.1.1 or version 3.1.2 of the Genome Aggregation Database. Based on the available evidence, the c.1142C>T (p.Thr381Ile) variant is classified as a variant of uncertain significance for methylmalonic aciduria, cblA type. |
Natera, |
RCV001339627 | SCV002084832 | uncertain significance | Methylmalonic aciduria, cblA type | 2020-03-04 | no assertion criteria provided | clinical testing |