Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000812265 | SCV000952573 | uncertain significance | Osteogenesis imperfecta type 8 | 2022-07-25 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 50 of the P3H1 protein (p.Asp50Asn). This variant is present in population databases (rs375176399, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with P3H1-related conditions. ClinVar contains an entry for this variant (Variation ID: 655976). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003489902 | SCV004241351 | uncertain significance | not specified | 2023-12-19 | criteria provided, single submitter | clinical testing | Variant summary: P3H1 c.148G>A (p.Asp50Asn) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.7e-05 in 229820 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.148G>A in individuals affected with Osteogenesis Imperfecta and no experimental evidence demonstrating its impact on protein function have been reported. One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| ARUP Laboratories, |
RCV000812265 | SCV004563389 | uncertain significance | Osteogenesis imperfecta type 8 | 2023-05-30 | criteria provided, single submitter | clinical testing | The P3H1 c.148G>A; p.Asp50Asn variant (rs375176399), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 655976). This variant is found in the general population with an allele frequency of 0.002% (5/261206 alleles) in the Genome Aggregation Database. Computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.261). Due to limited information, the clinical significance of this variant is uncertain at this time. |