Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Victorian Clinical Genetics Services, |
RCV002471717 | SCV002769209 | likely pathogenic | Intellectual disability, autosomal dominant 52 | 2020-05-21 | criteria provided, single submitter | clinical testing | A heterozygous missense variant was identified, NM_018489.2(ASH1L):c.4289G>T in exon 3 of the ASH1L gene. This substitution is predicted to create a major amino acid change from a glycine to a valine at position 1430 of the protein; NP_060959.2(ASH1L):p.(Gly1430Val). The glycine at this position has high conservation (100 vertebrates, UCSC), but is not situated in a known functional domain (NCBI, PDB). In silico software predictions of the pathogenicity of this variant are conflicting (PolyPhen2, SIFT, CADD, Mutation Taster). The variant is not present in the gnomAD population database. This variant has not previously been reported in clinical cases. Testing of this patient's parents has confirmed this variant is de novo. Based on information available at the time of curation, this variant has been classified as LIKELY PATHOGENIC. |