Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000476381 | SCV000544852 | benign | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2023-07-07 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV001095722 | SCV001251560 | uncertain significance | Marfan syndrome | 2020-01-22 | criteria provided, single submitter | clinical testing | The FBN1 c.5582G>A (p.Ser1861Asn) variant is a missense variant that has been reported in one study in which it was identified in a heterozygous state in one individual suspected of having Marfan syndrome but with insufficient clinical evidence for a confirmed diagnosis (Madar et al. 2019). The p.Ser1861Asn variant is reported at a frequency of 0.000026 in the European (non-Finnish) population of the Genome Aggregation Database. The Ser1861 residue is located in one of the 47 calcium-binding EGF-like domains of the fibrillin-1 protein. Based on the limited evidence, the p.Ser1861Asn variant is classified as a variant of unknown significance for Marfan syndrome. |
Color Diagnostics, |
RCV001181376 | SCV001346510 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2019-09-24 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with asparagine at codon 1861 of the FBN1 protein. Computational prediction tool suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold ≤0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has been reported in an individual affected with suspected Marfan syndrome or related fibrillinopathy (PMID: 31163209). This variant has also been identified in 4/250868 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Gene |
RCV001753875 | SCV001995456 | uncertain significance | not provided | 2019-09-03 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Although located in a calcium-binding EGF-like domain of the FBN1 gene, it does not affect a cysteine residue within this domain; cysteine substitutions in the calcium-binding EGF-like domains represent the majority of pathogenic missense changes associated with FBN1-related disorders (Collod-Beroud et al., 2003); Reported in ClinVar but additional evidence is not available (ClinVar Variant ID# 406289; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 31163209) |
Fulgent Genetics, |
RCV002502618 | SCV002806734 | uncertain significance | Ectopia lentis 1, isolated, autosomal dominant; Marfan syndrome; MASS syndrome; Stiff skin syndrome; Weill-Marchesani syndrome 2, dominant; Acromicric dysplasia; Geleophysic dysplasia 2; Progeroid and marfanoid aspect-lipodystrophy syndrome | 2022-04-05 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV001095722 | SCV004814646 | uncertain significance | Marfan syndrome | 2023-06-28 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with asparagine at codon 1861 of the FBN1 protein. Computational prediction tool suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <=0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has been reported in an individual affected with suspected Marfan syndrome or related fibrillinopathy (PMID: 31163209). This variant has also been identified in 4/250868 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |