Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000574725 | SCV000670650 | uncertain significance | Hereditary cancer-predisposing syndrome | 2016-05-02 | criteria provided, single submitter | clinical testing | The p.L1172P variant (also known as c.3515T>C), located in coding exon 13 of the PALB2 gene, results from a T to C substitution at nucleotide position 3515. The leucine at codon 1172 is replaced by proline, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6497 samples (12994 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 130000 alleles tested) in our clinical cohort. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV001853729 | SCV002287573 | uncertain significance | Familial cancer of breast | 2023-06-26 | criteria provided, single submitter | clinical testing | Experimental studies have shown that this missense change affects PALB2 function (PMID: 31757951, 33139182). 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. 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. ClinVar contains an entry for this variant (Variation ID: 484186). This variant has not been reported in the literature in individuals affected with PALB2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 1172 of the PALB2 protein (p.Leu1172Pro). |