Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ce |
RCV001357172 | SCV002496476 | likely benign | not provided | 2022-03-01 | criteria provided, single submitter | clinical testing | KDM1A: PP2, BS2 |
| Labcorp Genetics |
RCV001357172 | SCV003013957 | uncertain significance | not provided | 2024-10-28 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 95 of the KDM1A protein (p.Thr95Ala). This variant is present in population databases (rs200773378, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with KDM1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 1050172). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. |
| Ambry Genetics | RCV004988587 | SCV005610796 | likely benign | Inborn genetic diseases | 2024-11-23 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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. |
| Department of Pathology and Laboratory Medicine, |
RCV001357172 | SCV001552546 | likely benign | not provided | no assertion criteria provided | clinical testing | The KDM1A p.Thr95Ala variant was not identified in the literature nor was it identified in ClinVar, Cosmic or LOVD 3.0. The variant was identified in dbSNP (ID: rs200773378) and in control databases in 14 of 199878 chromosomes at a frequency of 0.00007 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: Other in 1 of 4894 chromosomes (freq: 0.000204) and European (non-Finnish) in 13 of 87160 chromosomes (freq: 0.000149); it was not observed in the African, Latino, Ashkenazi Jewish, East Asian, European (Finnish) or South Asian populations. The p.Thr95 residue is conserved in in mammals but not in more distantly related organisms however computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. |