Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003682117 | SCV004405097 | pathogenic | not provided | 2025-01-01 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu314Lysfs*4) in the MBD4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MBD4 are known to be pathogenic (PMID: 30049810, 35460607). 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 variant has not been reported in the literature in individuals affected with MBD4-related conditions. ClinVar contains an entry for this variant (Variation ID: 2807074). For these reasons, this variant has been classified as Pathogenic. |
Prevention |
RCV003981042 | SCV004798061 | likely pathogenic | MBD4-related disorder | 2024-10-03 | criteria provided, single submitter | clinical testing | To our knowledge, this variant has not been reported in the literature. This variant is reported in 1.1% of alleles in individuals of South Asian descent in gnomAD. This variant falls within a poly-adenine tract which is difficult to accurately sequence with NGS, thus allele frequency data should be interpreted with caution. Frameshift variants in MBD4 are expected to be pathogenic. This variant is interpreted as likely pathogenic. |
Ambry Genetics | RCV004985483 | SCV005617996 | benign | Inborn genetic diseases | 2024-11-21 | criteria provided, single submitter | clinical testing | This alteration is classified as 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. |