Submissions for variant NM_004523.4(KIF11):c.209T>C (p.Met70Thr)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Pittsburgh Clinical Genomics Laboratory, University of Pittsburgh Medical Center	RCV004784933	SCV005397197	uncertain significance	Microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability	2022-11-14	criteria provided, single submitter	clinical testing	This sequence variant is a single nucleotide substitution (T>C) at coding nucleotide 209 in the KIF11 gene which results in a methionine to threonine amino acid change at residue 70 in the KIF11 protein. This novel variant has not been reported previously in individuals with KIF11-related disease, to our knowledge. This variant is absent from the gnomAD control population database (0/~228000 alleles). Bioinformatic tools are inconsistent in their predictions if this variant is likely to be damaging or tolerated, though the Met70 residue is highly conserved in vertebrates. Additioly, splicing tools predict that this variant may affect the utilization of the exon 2 splice donor site. Functiol studies assessing the effect of this variant on protein structure or activity have not been performed, to our knowledge. At this time, there is insufficient evidence to determine if this variant is pathogenic or benign. Therefore, we consider it to be a variant of uncertain significance. ACMG Criteria: PM2