INVS was first reported in relation to autosomal recessive nephronophthisis-INVS in 2003 (Otto et al.; PMID: 12872123). At least 15 unique variants (missense, nonsense, frameshift) have been reported in 11 probands in 3 publications (PMIDs: 12872123, 19177160, 31706999). Evidence supporting this gene-disease relationship includes case-level data, segregation data, and experimental data. Variants in this gene segregated with disease in one Bedouin family with 10 segregations (Haider et al. 1998; PMID: 9792867). The mechanism for disease is biallelic loss of function. This gene-disease association is supported by animal models and an expression study (PMIDs: 9744276, 26615802, 15852005). In summary, there is definitive evidence to support the relationship between INVS and autosomal recessive nephronophthisis-INVS. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Cystic and Ciliopathy Expert Panel on the meeting date 2/24/21 (SOP Version 8).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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