Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000020298 | SCV000194345 | pathogenic | Lissencephaly due to LIS1 mutation | 2013-02-08 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000254776 | SCV000322237 | pathogenic | not provided | 2015-12-30 | criteria provided, single submitter | clinical testing | The c.1050delG pathogenic variant in the PAFAH1B1 gene has been reported previously in individuals with lissencephaly, seizures, and developmental delays (Uyanik et al., 2007; Saillour et al., 2009). The deletion causes a frameshift starting with codon Lysine 351, changes this amino acid to a Serine residue and creates a premature Stop codon at position 4 of the new reading frame, denoted p.Lys351SerfsX4. This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Additionally, it was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. |
Invitae | RCV000254776 | SCV002229937 | pathogenic | not provided | 2023-10-22 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Lys351Serfs*4) in the PAFAH1B1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PAFAH1B1 are known to be pathogenic (PMID: 1671808, 11115846, 14581661). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with lissencephaly (PMID: 17664403, 26494205). ClinVar contains an entry for this variant (Variation ID: 21176). For these reasons, this variant has been classified as Pathogenic. |
Ce |
RCV000254776 | SCV002498224 | pathogenic | not provided | 2022-02-01 | criteria provided, single submitter | clinical testing |