Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000669322 | SCV001146726 | uncertain significance | Phenylketonuria | 2019-09-29 | reviewed by expert panel | curation | The c.441+4A>G variant in PAH has been reported in an individual with PAH deficiency (PP4) with likely pathogenic variant p.Val230Ile (PM3-supporting) (PMID: 12655553); and an Iranian patient with PAH deficiency ( PMID: 28676969, 2nd variant not reported). This variant is absent in population databases (PM2). Computational evidence support a splicing effect (HSF and MaxEnt). In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PP4, PM2, PM3_supporting, PP3. |
Counsyl | RCV000669322 | SCV000794065 | uncertain significance | Phenylketonuria | 2017-09-07 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000669322 | SCV000814138 | pathogenic | Phenylketonuria | 2023-12-23 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 4 of the PAH gene. It does not directly change the encoded amino acid sequence of the PAH protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with PAH-related conditions (PMID: 12655553, 19015950, 28676969; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 102674). 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. |
Baylor Genetics | RCV000669322 | SCV005053846 | pathogenic | Phenylketonuria | 2023-11-12 | criteria provided, single submitter | clinical testing | |
De |
RCV000088922 | SCV000119520 | not provided | not provided | no assertion provided | not provided |