Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Victorian Clinical Genetics Services, |
RCV004787204 | SCV005398595 | uncertain significance | Synpolydactyly type 2 | 2019-08-28 | criteria provided, single submitter | clinical testing | A heterozygous missense variant, NM_006486.2(FBLN1):c.1949G>A, has been identified in exon 16 of 17 of the FBLN1 gene. The variant is predicted to result in a minor amino acid change from arginine to histidine at position 650 of the protein (NP_006477.2(FBLN1):p.(Arg650His). The arginine residue at this position has low conservation (100 vertebrates, UCSC), but is not located within a well established functional domain. In silico predictions of pathogenicity for this variant are conflicting (Polyphen, SIFT, CADD, Mutation Taster). The variant is present in the gnomAD database at a frequency of 0.0011% (3 heterozygotes). This variant has not been previously reported in clinical cases. Based on the information available at the time of curation, this variant has been classified as a VARIANT of UNCERTAIN SIGNIFICANCE (VUS) with LOW CLINICAL RELEVANCE. |