Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ce |
RCV001091656 | SCV001247828 | likely pathogenic | not provided | 2019-10-01 | criteria provided, single submitter | clinical testing | |
Institute of Medical Genetics and Applied Genomics, |
RCV001091656 | SCV001448043 | likely pathogenic | not provided | 2020-10-23 | criteria provided, single submitter | clinical testing | |
Institute for Genomic Statistics and Bioinformatics, |
RCV000250290 | SCV001519383 | pathogenic | Multiple congenital anomalies-hypotonia-seizures syndrome 1 | criteria provided, single submitter | clinical testing | The NM_176787:exon17:c.1434+5G>A splice site mutation is a known pathogenic variant that has been maternally inherited. | |
Invitae | RCV000250290 | SCV001576043 | pathogenic | Multiple congenital anomalies-hypotonia-seizures syndrome 1 | 2024-01-28 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 16 of the PIGN gene. It does not directly change the encoded amino acid sequence of the PIGN protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs369486176, gnomAD 0.004%). This variant has been observed in individual(s) with PIGN-related conditions (PMID: 26394714, 34051595, 35179230). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 264636). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Gene |
RCV001091656 | SCV001813893 | likely pathogenic | not provided | 2021-06-29 | criteria provided, single submitter | clinical testing | In silico analysis, which includes splice predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 31589614, 34051595, 27535533, 27038415, 26394714) |
Neuberg Supratech Reference Laboratories Pvt Ltd, |
RCV000250290 | SCV004100637 | likely pathogenic | Multiple congenital anomalies-hypotonia-seizures syndrome 1 | criteria provided, single submitter | clinical testing | The splice region variant c.1434+5G>A in PIGN (NM_176787.5) has been reported previously in affected indivduals (Fleming L et al). The variant as been submitted to ClinVar as Likely Pathogenic. The c.1434+5G>A variant is observed in 1/28,292 (0.0035%) alleles from individuals of South Asian background in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. The nucleotide c.1434+5G>A in PIGN is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Likely Pathogenic. | |
OMIM | RCV000250290 | SCV000320693 | pathogenic | Multiple congenital anomalies-hypotonia-seizures syndrome 1 | 2016-09-28 | no assertion criteria provided | literature only |