Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000171108 | SCV000223673 | uncertain significance | not provided | 2014-04-29 | criteria provided, single submitter | clinical testing | The F465S variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The F465S variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The F465S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. A missense mutation in a nearby residue (G460S) has been reported in association with sudden infant death syndrome, supporting the functional importance of this region of the protein. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in LQT panel(s). |
| Ambry Genetics | RCV000620667 | SCV000737617 | uncertain significance | Cardiovascular phenotype | 2016-07-13 | criteria provided, single submitter | clinical testing | The p.F465S variant (also known as c.1394T>C), located in coding exon 7 of the SNTA1 gene, results from a T to C substitution at nucleotide position 1394. The phenylalanine at codon 465 is replaced by serine, an amino acid with highly dissimilar properties. This variant was previously reported in the SNPDatabase as rs774908810. Based on data from ExAC, the C allele has an overall frequency less than 0.01% (1/106204). This variant was not reported in population based cohorts in the following databases: NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. This amino acid position is not well 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. |