Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000174739 | SCV000226101 | pathogenic | not provided | 2015-03-27 | criteria provided, single submitter | clinical testing | |
| Victorian Clinical Genetics Services, |
RCV002470793 | SCV002767020 | pathogenic | Kabuki syndrome 1 | 2022-09-02 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Kabuki syndrome 1 (MIM#147920). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0302 - Variant is present in gnomAD (v3) <0.001 for a dominant condition (1 heterozygotes, 0 homozygotes). (SP) 0701 - Other NMD-predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity (ClinVar). (SP) 0803 - This variant has limited previous evidence of pathogenicity in unrelated individuals. This variant has been classified as pathogenic by a clinical laboratory in ClinVar, and identified in an individual with Kabuki syndrome in the literature (PMID: 23320472). (SP) 1203 - This variant has been shown to be de novo in the proband (parental status confirmed by trio analysis). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
| Labcorp Genetics |
RCV003588588 | SCV004295044 | pathogenic | Kabuki syndrome | 2023-07-31 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ala1390Glyfs*42) in the KMT2D gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in KMT2D are known to be pathogenic (PMID: 22126750). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with clinical features of Kabuki syndrome and/or cardiac findings (PMID: 23320472, 30287924). ClinVar contains an entry for this variant (Variation ID: 194381). For these reasons, this variant has been classified as Pathogenic. |