Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001765796 | SCV001999448 | uncertain significance | not provided | 2020-10-15 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Labcorp Genetics |
RCV001765796 | SCV002988632 | uncertain significance | not provided | 2022-11-22 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs758545508, gnomAD 0.004%). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1810 of the USP9X protein (p.Ile1810Val). This variant has not been reported in the literature in individuals affected with USP9X-related conditions. ClinVar contains an entry for this variant (Variation ID: 1309627). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. |
| Ambry Genetics | RCV003163860 | SCV003886763 | uncertain significance | Inborn genetic diseases | 2023-01-10 | criteria provided, single submitter | clinical testing | The c.5428A>G (p.I1810V) alteration is located in exon 35 (coding exon 34) of the USP9X gene. This alteration results from a A to G substitution at nucleotide position 5428, causing the isoleucine (I) at amino acid position 1810 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Victorian Clinical Genetics Services, |
RCV004785301 | SCV005398069 | uncertain significance | Intellectual disability, X-linked 99 | 2024-09-22 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3B. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with X-linked intellectual developmental disorder 99 (MIM#300919) and X-linked syndromic female-restricted intellectual developmental disorder 99 (MIM#300968). (I) 0108 - This gene is associated with both X-linked recessive and X-linked dominant disease. Partial loss of function variants are inherited in a X-linked recessive pattern, affecting predominantly males. Complete loss of function variants are inherited in a X-linked dominant pattern and are more severe, affecting only females (PMID: 31443933, PMID: 26833328). (I) 0200 - Variant is predicted to result in a missense amino acid change from isoleucine to valine. (I) 0253 - This variant is hemizygous. (I) 0304 - Variant is present in gnomAD <0.01 (v2: 2 heterozygotes, 0 homozygotes, 0 hemizygotes). (SP) 0503 - Missense variant consistently predicted to be tolerated by multiple in silico tools or not conserved in placental mammals with a minor amino acid change. (SB) 0603 - Missense variant in a region that is highly intolerant to missense variation (high constraint region in DECIPHER). (SP) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0809 - Previous evidence of pathogenicity for this variant is inconclusive. This variant has been reported three times as VUS in ClinVar. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1205 - This variant has been shown to be maternally inherited (by trio analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |