Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Mendelics | RCV000990081 | SCV001140868 | uncertain significance | Familial amyloid neuropathy | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Molecular Genetics Laboratory, |
RCV001173302 | SCV001336386 | uncertain significance | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing | ||
Invitae | RCV000990081 | SCV002122598 | uncertain significance | Familial amyloid neuropathy | 2023-12-06 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 4 of the TTR protein (p.His4Leu). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with TTR-related conditions. ClinVar contains an entry for this variant (Variation ID: 803480). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
Ambry Genetics | RCV002346195 | SCV002641521 | uncertain significance | Cardiovascular phenotype | 2019-12-14 | criteria provided, single submitter | clinical testing | The p.H4L variant (also known as c.11A>T), located in coding exon 1 of the TTR gene, results from an A to T substitution at nucleotide position 11. The histidine at codon 4 is replaced by leucine, an amino acid with similar properties. This variant was listed as a variant of unknown significance identified in a population database (Lahuerta Pueyo C et al. Eur. J. Hum. Genet., 2019 May;27:783-791). This amino acid position is not well conserved in available vertebrate species, and leucine is the reference amino acid in other 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. |