Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001919355 | SCV002187704 | uncertain significance | Bloom syndrome | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine with phenylalanine at codon 1170 of the BLM protein (p.Tyr1170Phe). The tyrosine residue is highly conserved and there is a small physicochemical difference between tyrosine and phenylalanine. This variant is present in population databases (rs746692894, ExAC 0.01%). This variant has not been reported in the literature in individuals affected with BLM-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). 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 | RCV002458813 | SCV002613684 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-08-07 | criteria provided, single submitter | clinical testing | The p.Y1170F variant (also known as c.3509A>T), located in coding exon 17 of the BLM gene, results from an A to T substitution at nucleotide position 3509. The tyrosine at codon 1170 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |