Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001283978 | SCV001469511 | pathogenic | not provided | 2020-02-14 | criteria provided, single submitter | clinical testing | Predicted to have a damaging effect on the protein. One other pathogenic variant affects the same amino acid. In multiple individuals, this variant has been seen with a single recessive pathogenic variant in the same gene, suggesting this variant may also be pathogenic. Assessment of experimental evidence suggests this variant results in abnormal protein function. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003331101 | SCV004037694 | pathogenic | alpha Thalassemia | 2023-08-29 | criteria provided, single submitter | clinical testing | Variant summary: HBA1 c.178G>C (p.Gly60Arg) results in a non-conservative amino acid change located in the Globin domain (IPR000971) of the encoded protein sequence. Four of four in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 7.4e-06 in 135930 control chromosomes (gnomAD). c.178G>C has been reported in the literature in multiple individuals affected with Alpha Thalassemia (e.g. Oron-Karni_2000, Fang_2014, Jiang_2017, Gilad_2017). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. However, in silico protein folding models predict that the variant is unstable in both oxy and de-oxy environments (Scheps_2019). The following publications have been ascertained in the context of this evaluation (PMID: 24261598, 28160324, 29115167, 11074535, 31553106). One ClinVar submitter has assessed the variant since 2014, and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |