Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000432045 | SCV000536287 | uncertain significance | not provided | 2020-10-16 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Baylor Genetics | RCV001335345 | SCV001528475 | uncertain significance | Lethal left ventricular non-compaction-seizures-hypotonia-cataract-developmental delay syndrome | 2018-02-02 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
| Fulgent Genetics, |
RCV001335345 | SCV002815000 | uncertain significance | Lethal left ventricular non-compaction-seizures-hypotonia-cataract-developmental delay syndrome | 2021-08-04 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000432045 | SCV003264665 | uncertain significance | not provided | 2024-01-02 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 682 of the MIPEP protein (p.Gly682Asp). This variant is present in population databases (rs150308123, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with MIPEP-related conditions. ClinVar contains an entry for this variant (Variation ID: 392943). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004689738 | SCV005186038 | uncertain significance | not specified | 2024-05-02 | criteria provided, single submitter | clinical testing | Variant summary: MIPEP c.2045G>A (p.Gly682Asp) results in a non-conservative amino acid change located in the Peptidase M3A/M3B catalytic domain (IPR001567) of the encoded protein sequence, in the first nucleotide of exon 19 adjacent to the intron 18 / exon 19 3' splice acceptor site. Three of five in-silico tools predict a benign effect of the variant on protein function. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a cryptic 5' donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0007 in 245244 control chromosomes. To our knowledge, no occurrence of c.2045G>A in individuals affected with Lethal Left Ventricular Non-Compaction Delay Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 392943). Based on the evidence outlined above, the variant was classified as uncertain significance. |