Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Victorian Clinical Genetics Services, |
RCV002470400 | SCV002767794 | uncertain significance | Intellectual disability-severe speech delay-mild dysmorphism syndrome | 2019-08-28 | criteria provided, single submitter | clinical testing | A heterozygous missense variant was identified, NM_032682.5(FOXP1):c.1223C>T in exon 15 of 21 of the FOXP1 gene. This substitution is predicted to create a moderate amino acid change from threonine to methionine at position 408 of the protein, NP_116071.2(FOXP1):p.(Thr408Met). The threonine at this position has very high conservation (100 vertebrates, UCSC), but is not situated in a known functional domain. In silico software predicts this variant to be pathogenic (PolyPhen, SIFT, CADD, MutationTaster). The variant is not present in the gnomAD population database, however, an alternative change to serine at the same residue has been reported in the gnomAD database at a frequency of 0.013%. The variant has not previously been reported in clinical cases. Based on information available at the time of curation, this variant has been classified as a VARIANT of UNCERTAIN SIGNIFICANCE (VUS). |