Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000220750 | SCV000274802 | uncertain significance | Hereditary cancer-predisposing syndrome | 2015-11-18 | criteria provided, single submitter | clinical testing | The p.L148H variant (also known as c.443T>A), located in coding exon 4 of the APC gene, results from a T to A substitution at nucleotide position 443. The leucine at codon 148 is replaced by histidine, an amino acid with some 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 6489 samples (12978 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.003% (greater than 70000 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 p.L148H remains unclear. |
Invitae | RCV003534513 | SCV000816823 | uncertain significance | Familial adenomatous polyposis 1 | 2022-08-09 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 231065). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is present in population databases (rs762062860, gnomAD 0.0009%). This sequence change replaces leucine, which is neutral and non-polar, with histidine, which is basic and polar, at codon 148 of the APC protein (p.Leu148His). |