Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002017488 | SCV002287546 | uncertain significance | Acrocallosal syndrome | 2022-10-24 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 881 of the KIF7 protein (p.Thr881Met). This variant is present in population databases (rs372660203, gnomAD 0.04%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with KIF7-related conditions. ClinVar contains an entry for this variant (Variation ID: 1501465). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on KIF7 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Fulgent Genetics, |
RCV002498012 | SCV002814341 | uncertain significance | Acrocallosal syndrome; Multiple epiphyseal dysplasia, Al-Gazali type; Hydrolethalus syndrome 2 | 2021-07-21 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002657662 | SCV003548547 | uncertain significance | Inborn genetic diseases | 2020-11-13 | criteria provided, single submitter | clinical testing | The c.2642C>T (p.T881M) alteration is located in exon 13 (coding exon 12) of the KIF7 gene. This alteration results from a C to T substitution at nucleotide position 2642, causing the threonine (T) at amino acid position 881 to be replaced by a methionine (M). Based on data from the Genome Aggregation Database (gnomAD) database, the KIF7 c.2642C>T alteration was observed in 0.01% (22/219568) of total alleles studied. This amino acid position is highly conserved in available vertebrate species. The p.T881M alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Gene |
RCV003327551 | SCV004034701 | uncertain significance | not provided | 2023-03-06 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |