Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000811826 | SCV000952113 | uncertain significance | Dyskeratosis congenita | 2024-10-26 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 344 of the TINF2 protein (p.Pro344Ser). This variant is present in population databases (rs200454893, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with TINF2-related conditions. ClinVar contains an entry for this variant (Variation ID: 655611). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Possibly Damaging". The serine 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. |
| Fulgent Genetics, |
RCV005004445 | SCV002780873 | uncertain significance | Revesz syndrome; Dyskeratosis congenita, autosomal dominant 3 | 2024-06-10 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV005240607 | SCV005884433 | uncertain significance | not specified | 2024-12-26 | criteria provided, single submitter | clinical testing | Variant summary: TINF2 c.1030C>T (p.Pro344Ser) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 249568 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1030C>T in individuals affected with TINF2-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 655611). Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Gene |
RCV005409748 | SCV006075675 | uncertain significance | not provided | 2024-10-29 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |