Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
EGL Genetic Diagnostics, |
RCV000334194 | SCV000339617 | uncertain significance | not provided | 2016-02-12 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000541582 | SCV000657805 | uncertain significance | Charcot-Marie-Tooth disease, type 2 | 2019-05-31 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with asparagine at codon 553 of the LMNA protein (p.Asp553Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs373671419, ExAC no frequency). This variant has been reported in an individual affected with LMNA-related disease (PMID: 27884249). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15". The asparagine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, |
RCV000622473 | SCV000740349 | uncertain significance | Arrhythmogenic right ventricular cardiomyopathy | 2016-11-29 | criteria provided, single submitter | clinical testing | |
Laboratory for Molecular Medicine, |
RCV000825772 | SCV000967237 | likely benign | not specified | 2019-03-10 | criteria provided, single submitter | clinical testing | The p.Asp553Asn variant in LMNA is classified as likely benign because it has been identified in 0.06% (15/24926) of Latino chromosomes by gnomAD (http://gnomad.broadinstitute.org). Additionally, 2 mammals (rat and mouse) have an asparagine (Asn) at this position despite relatively nearby amino acid conservation. In addition, most computational tools do not suggest a high likelihood of impact to the protein. ACMG/AMP Criteria applied: BS1_supporting, BP4. |
Molecular Genetics Laboratory, |
RCV001172624 | SCV001335687 | uncertain significance | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing | ||
Color | RCV001183038 | SCV001348688 | likely benign | Cardiomyopathy | 2019-10-18 | criteria provided, single submitter | clinical testing |