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Cerebral vascular malformations v3.36 NOS3 Achchuthan Shanmugasundram Classified gene: NOS3 as Amber List (moderate evidence)
Cerebral vascular malformations v3.36 NOS3 Achchuthan Shanmugasundram Gene: nos3 has been classified as Amber List (Moderate Evidence).
Cerebral vascular malformations v3.35 NOS3 Achchuthan Shanmugasundram Tag watchlist tag was added to gene: NOS3.
Cerebral vascular malformations v3.35 NOS3 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: As reviewed by Alexandra Njegic, there are two unrelated cases and some functional evidence available for the association of biallelic variants with MMA. However, there is only one case with monoallelic NOS3 variant. The pathogenicity of this monoallelic variant was not explored in detail in the publication.

Hence, the gene should be rated amber and the MOI should be set to BIALLELIC.

The 'watchlist' tag has been added to review this gene in light of new evidence.
Cerebral vascular malformations v3.35 NOS3 Achchuthan Shanmugasundram Mode of inheritance for gene: NOS3 was changed from Other to BIALLELIC, autosomal or pseudoautosomal
Cerebral vascular malformations v3.34 NOS3 Achchuthan Shanmugasundram Publications for gene: NOS3 were set to 37383439; 36941667
Cerebral vascular malformations v3.33 NOS3 Achchuthan Shanmugasundram Phenotypes for gene: NOS3 were changed from Moyamoya Disease; Moyamoya Angiopathy to Moyamoya disease, MONDO:0016820
Cerebral vascular malformations v3.32 NOS3 Achchuthan Shanmugasundram reviewed gene: NOS3: Rating: AMBER; Mode of pathogenicity: None; Publications: 36941667, 37383439; Phenotypes: Moyamoya disease, MONDO:0016820; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral vascular malformations v3.20 NOS3 Alexandra Njegic changed review comment from: Conflicting reports of mode of inheritance.
37383439: 1/6 Moyamoya disease patients with a NOS3 heterozygous variant, pathogenicity not provided.
36941667: 6 probands from consanguineous parentage with MMA, 2 NOS3 homozygous variants. In vitro studies, splice donor site variant leads to lack of eNOS in endothelial progenitor cells derived from the affected proband. Missense variant leads to reduced eNOS protein expression (HEK cells).
Sources: Literature; to: 2 papers with a different mode of inheritance shown; pathogenicity of AD variant not explored in detail.
37383439: 1/6 Moyamoya disease patients with a NOS3 heterozygous variant, pathogenicity not provided.
36941667: 6 probands from consanguineous parentage with MMA, 2 NOS3 homozygous variants. In vitro studies, splice donor site variant leads to lack of eNOS in endothelial progenitor cells derived from the affected proband. Missense variant leads to reduced eNOS protein expression (HEK cells).
Sources: Literature
Cerebral vascular malformations v3.18 NOS3 Alexandra Njegic gene: NOS3 was added
gene: NOS3 was added to Cerebral vascular malformations. Sources: Literature
Mode of inheritance for gene: NOS3 was set to Other
Publications for gene: NOS3 were set to 37383439; 36941667
Phenotypes for gene: NOS3 were set to Moyamoya Disease; Moyamoya Angiopathy
Penetrance for gene: NOS3 were set to unknown
Review for gene: NOS3 was set to AMBER
Added comment: Conflicting reports of mode of inheritance.
37383439: 1/6 Moyamoya disease patients with a NOS3 heterozygous variant, pathogenicity not provided.
36941667: 6 probands from consanguineous parentage with MMA, 2 NOS3 homozygous variants. In vitro studies, splice donor site variant leads to lack of eNOS in endothelial progenitor cells derived from the affected proband. Missense variant leads to reduced eNOS protein expression (HEK cells).
Sources: Literature