Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000652765 | SCV000774636 | uncertain significance | Autosomal dominant nonsyndromic hearing loss 1; Progressive microcephaly-seizures-cortical blindness-developmental delay syndrome | 2023-12-09 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 1033 of the DIAPH1 protein (p.Asp1033Asn). This variant is present in population databases (no rsID available, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with DIAPH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 542359). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001269256 | SCV001448581 | uncertain significance | not specified | 2020-11-04 | criteria provided, single submitter | clinical testing | Variant summary: DIAPH1 c.3097G>A (p.Asp1033Asn) results in a conservative amino acid change located in the FH2 (formin homology) domain (IPR015425) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 249432 control chromosomes (gnomAD). 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.3097G>A in individuals affected with Seizures, Cortical Blindness, and Microcephaly Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |