Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000520951 | SCV000621633 | uncertain significance | not provided | 2017-10-24 | criteria provided, single submitter | clinical testing | The N686K variant in the LTBP3 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. Although not observed in the homozygous state, the N686K variant is observed in 47/30780 (0.15%) alleles from individuals of South Asian background in large population cohorts (Lek et al., 2016). The N686K variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is not conserved. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret N686K as a variant of uncertain significance. |
Labcorp Genetics |
RCV001858040 | SCV002205297 | uncertain significance | Brachyolmia-amelogenesis imperfecta syndrome | 2023-04-22 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 452796). This variant has not been reported in the literature in individuals affected with LTBP3-related conditions. This variant is present in population databases (rs376337792, gnomAD 0.2%). This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 686 of the LTBP3 protein (p.Asn686Lys). |
Ambry Genetics | RCV002420324 | SCV002727595 | likely benign | Inborn genetic diseases | 2021-11-09 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Revvity Omics, |
RCV000520951 | SCV003812784 | uncertain significance | not provided | 2022-11-22 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV003962455 | SCV004784613 | likely benign | LTBP3-related disorder | 2022-09-28 | no assertion criteria provided | clinical testing | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |