Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001850028 | SCV002181912 | uncertain significance | not provided | 2025-01-15 | criteria provided, single submitter | clinical testing | This sequence change replaces tryptophan, which is neutral and slightly polar, with leucine, which is neutral and non-polar, at codon 21 of the MFAP5 protein (p.Trp21Leu). This variant is present in population databases (rs724159961, gnomAD 0.09%). This missense change has been observed in individual(s) with thoracic aortic aneurysm and dissection (PMID: 25434006). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 162200). 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 disruptive. Experimental studies have shown that this missense change affects MFAP5 function (PMID: 25434006). 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004767094 | SCV005380601 | likely benign | not specified | 2024-08-12 | criteria provided, single submitter | clinical testing | Variant summary: MFAP5 c.62G>T (p.Trp21Leu) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 3.4e-05 in 1611808 control chromosomes. The observed variant frequency is approximately 2.68 fold of the estimated maximal expected allele frequency for a pathogenic variant in MFAP5 causing Thoracic Aortic Aneurysms And Dissections phenotype (1.3e-05). c.62G>T has been reported in the literature in the heterozygous state in at least 1 family affected with Thoracic Aortic Aneurysms And Dissections (example, Barbier_2014, Arnaud_2019). At least 1 family showed possible, but not compelling, evidence of segregation (example, Barbier_2014). These data do not allow any conclusion about variant significance. At least one publication reports experimental evidence evaluating an impact on protein function. Fibroblasts from affected individual showed decreased protein levels of MFAP5, as did in vitro experiments in HEK cells (example, Barbier_2014). The following publications have been ascertained in the context of this evaluation (PMID: 30739908, 25434006). ClinVar contains an entry for this variant (Variation ID: 162200). Based on the evidence outlined above, the variant was classified as likely benign. |
| OMIM | RCV000149580 | SCV000196556 | pathogenic | Aortic aneurysm, familial thoracic 9 | 2014-12-04 | no assertion criteria provided | literature only |