Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000489398 | SCV000577564 | uncertain significance | not provided | 2018-03-15 | criteria provided, single submitter | clinical testing | The G11A variant has been published previously in association with a synpolydactyly phenotype; the homozygous proband was more severely affected than the heterozygous mother, but the father's phenotype was not provided (Brison et al., 2012). However, the variant has also been observed in the homozygous state at GeneDx in an individual whose phenotype did not match a HOXD13 presentation. The variant is observed in 3/1714 (0.175%) alleles from individuals of South Asian background in the ExAC dataset (Lek et al., 2016). G11A is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved in mammals; however, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Functional studies have shown that G11A has no effect on DNA binding, transactivation, or localization; however, it speeds protein degradation and led to skeletal abnormalities in chick embryos (Brison et al., 2012). In summary, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Invitae | RCV000489398 | SCV003500893 | benign | not provided | 2022-09-21 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000210944 | SCV000267634 | pathogenic | Synpolydactyly type 1 | 2018-07-20 | no assertion criteria provided | literature only |