Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001957229 | SCV002205438 | uncertain significance | not provided | 2021-12-03 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 504 of the MME protein (p.Glu504Val). This variant is present in population databases (rs201239248, gnomAD 0.003%). This missense change has been observed in individual(s) with MME-related conditions (PMID: 33144514). 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 tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 | RCV002560467 | SCV003654751 | uncertain significance | Inborn genetic diseases | 2022-11-15 | criteria provided, single submitter | clinical testing | The c.1511A>T (p.E504V) alteration is located in exon 16 (coding exon 15) of the MME gene. This alteration results from an A to T substitution at nucleotide position 1511, causing the glutamic acid (E) at amino acid position 504 to be replaced by a valine (V). Based on data from gnomAD, the T allele has an overall frequency of 0.002% (4/250594) total alleles studied. This amino acid position is well conserved in available vertebrate species. The in silico prediction for this alteration is inconclusive. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Genome |
RCV002560468 | SCV003761503 | not provided | Charcot-Marie-Tooth disease axonal type 2T; Spinocerebellar ataxia 43 | no assertion provided | phenotyping only | Variant classified as Uncertain significance and reported on 08-30-2021 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. |