Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000628652 | SCV000749556 | uncertain significance | Bloom syndrome | 2022-10-18 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 212 of the BLM protein (p.Ser212Phe). This variant is present in population databases (rs777938065, gnomAD 0.003%). This missense change has been observed in individual(s) with breast cancer (PMID: 23028338). ClinVar contains an entry for this variant (Variation ID: 524788). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The phenylalanine 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. |
Mendelics | RCV000628652 | SCV001139690 | uncertain significance | Bloom syndrome | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV001025173 | SCV001187311 | likely benign | Hereditary cancer-predisposing syndrome | 2021-04-28 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Natera, |
RCV000628652 | SCV002089957 | uncertain significance | Bloom syndrome | 2018-05-17 | no assertion criteria provided | clinical testing |