Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV004788363 | SCV005400157 | uncertain significance | Neurodevelopmental disorder | 2023-07-16 | 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 nephrotic syndrome (MONDO#0005377), ITSN1-related, and neurodevelopmental disorder (MONDO#0700092), ITSN1-related. (I) 0108 - This gene is associated with both recessive and dominant disease. Biallelic variants cause autosomal recessive nephrotic syndrome (MONDO#0005377), ITSN1-related, while monoallelic variants cause autosomal dominant neurodevelopmental disorder (MONDO#0700092), ITSN1-related (PMIDs: 29773874, 30721404, 34707297). (I) 0200 - Variant is predicted to result in a missense amino acid change from tryptophan to arginine. (I) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD (v2) <0.01 (1 heterozygote, 0 homozygotes). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0600 - Variant is located in the annotated cytoskeletal-regulatory complex EF hand domain (DECIPHER). (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0807 - This variant has no previous evidence of pathogenicity. (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) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |