Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000248004 | SCV000318738 | uncertain significance | Cardiovascular phenotype | 2013-06-13 | criteria provided, single submitter | clinical testing | The p.E252D variant (also known as c.756G>T) is located in coding exon 6 of the FBN2 gene. This alteration results from a G to T substitution at nucleotide position 756. The glutamic acid at codon 252 is replaced by aspartic acid, an amino acid with highly similar properties. This variant was observed in the unaffected parent of a female proband tested by our laboratory. The proband's clinical features included aortic dilatation, gross motor delay, short stature, facial asymmetry, pectus excavatum, strabisum, plagiocephaly and joint hyperlaxity. This variant was not reported in population-based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP) and 1000 Genomes Project. Based on protein sequence alignment, this amino acid position is highly conserved in available vertebrate species. This alteration is predicted to be probably damaging and deleterious by PolyPhen and SIFT in silico analyses, respectively. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. |