Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001019431 | SCV001180789 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-03-31 | criteria provided, single submitter | clinical testing | The p.A32T variant (also known as c.94G>A), located in coding exon 1 of the FH gene, results from a G to A substitution at nucleotide position 94. The alanine at codon 32 is replaced by threonine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Prevention |
RCV003411951 | SCV004114362 | uncertain significance | FH-related condition | 2022-12-12 | criteria provided, single submitter | clinical testing | The FH c.94G>A variant is predicted to result in the amino acid substitution p.Ala32Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0039% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-241682929-C-T) and is reported as uncertain significance in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/823298/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
| Invitae | RCV003769514 | SCV004624893 | uncertain significance | not provided | 2022-12-20 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with FH-related conditions. 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt FH protein function. ClinVar contains an entry for this variant (Variation ID: 823298). 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 sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 32 of the FH protein (p.Ala32Thr). |