Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000725985 | SCV000341014 | uncertain significance | not provided | 2016-05-10 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV000397767 | SCV000458119 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 49 | 2018-01-12 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Laboratory for Molecular Medicine, |
RCV000393069 | SCV000711100 | uncertain significance | not specified | 2016-04-21 | criteria provided, single submitter | clinical testing | The p.Pro59Leu variant in MARVELD2 has not been previously reported in individua ls with hearing loss, but it has been identified in 0.1% (51/66680) of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitut e.org; dbSNP rs150434290). Although this variant has been seen in the general po pulation, its frequency is not high enough to rule out a pathogenic role. Comput ational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Pro59Leu variant is uncertain. |
| Gene |
RCV000725985 | SCV000984630 | likely benign | not provided | 2020-12-16 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000725985 | SCV002138245 | uncertain significance | not provided | 2022-07-20 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 59 of the MARVELD2 protein (p.Pro59Leu). This variant is present in population databases (rs150434290, gnomAD 0.09%), 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 MARVELD2-related conditions. ClinVar contains an entry for this variant (Variation ID: 287288). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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. |