Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000414424 | SCV000490747 | pathogenic | not provided | 2025-01-14 | criteria provided, single submitter | clinical testing | In silico analysis supports a deleterious effect on protein structure/function; In silico analysis also suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown; This variant is associated with the following publications: (PMID: 25152457, 32077105, 30293248, 26960553, 30214071, 32579715, 39638571) |
| Labcorp Genetics |
RCV000819927 | SCV000960614 | pathogenic | Neu-Laxova syndrome 2 | 2024-12-31 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 99 of the PSAT1 protein (p.Ala99Val). 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 missense change has been observed in individuals with Neu-Laxova syndrome (PMID: 25152457, 30214071, 32579715). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 372478). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects PSAT1 function (PMID: 32077105). For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV005238963 | SCV005887218 | pathogenic | PSAT1-related disorder | 2025-01-15 | criteria provided, single submitter | clinical testing | Variant summary: PSAT1 c.296_297delinsTG (p.Ala99Val) results in a non-conservative amino acid change located in the PSAT_like domain (IPR022278) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00015 in 282872 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in PSAT1 causing PSAT1-Related Disorders, allowing no conclusion about variant significance. c.296_297delinsTG has been reported in the literature in multiple individuals affected with Neu-Laxova Syndrome (example, Acuna-Hidalgo_2014). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 31589614, 25152457). ClinVar contains an entry for this variant (Variation ID: 372478). Based on the evidence outlined above, the variant was classified as pathogenic. |