Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000386775 | SCV000393493 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2016-06-14 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000292634 | SCV000393494 | uncertain significance | Loeys-Dietz syndrome | 2016-06-14 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000386775 | SCV001412874 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2021-08-24 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with phenylalanine at codon 308 of the SMAD3 protein (p.Leu308Phe). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant is present in population databases (rs764656928, ExAC 0.02%). This variant has not been reported in the literature in individuals affected with SMAD3-related conditions. ClinVar contains an entry for this variant (Variation ID: 316862). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; 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. |
Color Diagnostics, |
RCV000386775 | SCV002053319 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2023-08-09 | criteria provided, single submitter | clinical testing | This missense variant replaces leucine with phenylalanine at codon 308 of the SMAD3 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with SMAD3-related disorders in the literature. This variant has been identified in 13/251476 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. |
Ambry Genetics | RCV003343776 | SCV004074301 | uncertain significance | Inborn genetic diseases | 2023-07-11 | criteria provided, single submitter | clinical testing | The c.922C>T (p.L308F) alteration is located in exon 7 (coding exon 7) of the SMAD3 gene. This alteration results from a C to T substitution at nucleotide position 922, causing the leucine (L) at amino acid position 308 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |