Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000187756 | SCV000241353 | likely benign | not provided | 2019-03-28 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000467580 | SCV000548807 | uncertain significance | Koolen-de Vries syndrome | 2021-07-13 | criteria provided, single submitter | clinical testing | Due to the possible presence of a polymorphic segmental duplication, the location of the variant could not be unambiguously resolved. Variants with ambiguous mapping are still reported relative to the KANSL1 transcript. This sequence change replaces histidine with arginine at codon 167 of the KANSL1 protein (p.His167Arg). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and arginine. The frequency data for this variant in the population databases (ExAC) is considered unreliable due to the presence of homologous sequence, such as pseudogenes or paralogs, in the genome. This variant has not been reported in the literature in individuals with KANSL1-related conditions. ClinVar contains an entry for this variant (Variation ID: 205768). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. Until the location of this sequence change can be resolved, the clinical significance of this variant remains uncertain. It has been classified as a Variant of Uncertain Significance. |
Ambry Genetics | RCV002514011 | SCV003617958 | likely benign | Inborn genetic diseases | 2021-10-29 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |