Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000445651 | SCV000791082 | likely pathogenic | beta Thalassemia | 2017-04-25 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000781440 | SCV000919460 | uncertain significance | not specified | 2018-05-30 | criteria provided, single submitter | clinical testing | Variant summary: HBB c.316-7C>G alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 3/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4.1e-06 in 246028 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.316-7C>G has been reported in the literature in unaffected heterozygous carriers and an individual affected with mild Beta Thalassemia intermedia. These data do not allow any conclusion about variant significance. One publication tested the effect of mutation in the pyrimidine tract of intron 2 of HBB and showed that changes in this region affected 3' end processing; however, the variant was tested in conjunction with other variants, so the specific effect of the variant is unknown (Millevoi_2002). Both ithanet and GeneReviews classified the variant as pathogenic/causal while multiple papers noted variant as a silent BTHAL mtuation. HbVar noted variant with various phenotypes (silent or mild thalasemia) when associated with different alleles. Based on the evidence outlined above, the variant was classified as uncertain significance until additional clinical data is reported. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001284152 | SCV001469778 | uncertain significance | not provided | 2019-11-12 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001284152 | SCV003439765 | likely benign | not provided | 2022-03-08 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000445651 | SCV000537298 | not provided | beta Thalassemia | no assertion provided | literature only |