TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27465	82618;82619;82620	chr2:178563739;178563738;178563737	chr2:179428466;179428465;179428464
N2AB	25824	77695;77696;77697	chr2:178563739;178563738;178563737	chr2:179428466;179428465;179428464
N2A	24897	74914;74915;74916	chr2:178563739;178563738;178563737	chr2:179428466;179428465;179428464
N2B	18400	55423;55424;55425	chr2:178563739;178563738;178563737	chr2:179428466;179428465;179428464
Novex-1	18525	55798;55799;55800	chr2:178563739;178563738;178563737	chr2:179428466;179428465;179428464
Novex-2	18592	55999;56000;56001	chr2:178563739;178563738;178563737	chr2:179428466;179428465;179428464
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-87
• Domain position: 97
• Structural Position: 132
• Q(SASA): 1.2871
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
N/H	None	None	0.938	N	0.605	0.323	0.318252033908	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
N/A	0.676	likely_pathogenic	0.6462	pathogenic	-0.23	Destabilizing	0.587	D	0.587	neutral	None	None	None	None	N
N/C	0.6624	likely_pathogenic	0.6312	pathogenic	0.406	Stabilizing	0.996	D	0.87	deleterious	None	None	None	None	N
N/D	0.1952	likely_benign	0.1655	benign	None	Stabilizing	0.007	N	0.357	neutral	N	0.457921493	None	None	N
N/E	0.8465	likely_pathogenic	0.807	pathogenic	-0.051	Destabilizing	0.587	D	0.65	prob.neutral	None	None	None	None	N
N/F	0.7819	likely_pathogenic	0.7624	pathogenic	-0.702	Destabilizing	0.984	D	0.736	deleterious	None	None	None	None	N
N/G	0.769	likely_pathogenic	0.7301	pathogenic	-0.373	Destabilizing	0.74	D	0.653	prob.neutral	None	None	None	None	N
N/H	0.2157	likely_benign	0.2085	benign	-0.455	Destabilizing	0.938	D	0.605	neutral	N	0.491765488	None	None	N
N/I	0.4706	ambiguous	0.44	ambiguous	0.053	Stabilizing	0.938	D	0.788	deleterious	N	0.490969021	None	None	N
N/K	0.8471	likely_pathogenic	0.8091	pathogenic	0.112	Stabilizing	0.007	N	0.377	neutral	N	0.486952869	None	None	N
N/L	0.4349	ambiguous	0.4211	ambiguous	0.053	Stabilizing	0.909	D	0.652	prob.neutral	None	None	None	None	N
N/M	0.6647	likely_pathogenic	0.6332	pathogenic	0.394	Stabilizing	0.996	D	0.739	deleterious	None	None	None	None	N
N/P	0.7647	likely_pathogenic	0.7544	pathogenic	-0.016	Destabilizing	0.953	D	0.762	deleterious	None	None	None	None	N
N/Q	0.7891	likely_pathogenic	0.75	pathogenic	-0.29	Destabilizing	0.909	D	0.651	prob.neutral	None	None	None	None	N
N/R	0.8554	likely_pathogenic	0.8227	pathogenic	0.182	Stabilizing	0.833	D	0.615	neutral	None	None	None	None	N
N/S	0.1437	likely_benign	0.1373	benign	-0.023	Destabilizing	0.682	D	0.689	prob.delet.	D	0.529821664	None	None	N
N/T	0.4255	ambiguous	0.3725	ambiguous	0.052	Stabilizing	0.682	D	0.651	prob.neutral	N	0.473888236	None	None	N
N/V	0.5547	ambiguous	0.5128	ambiguous	-0.016	Destabilizing	0.909	D	0.78	deleterious	None	None	None	None	N
N/W	0.9424	likely_pathogenic	0.9375	pathogenic	-0.751	Destabilizing	0.996	D	0.876	deleterious	None	None	None	None	N
N/Y	0.3707	ambiguous	0.342	ambiguous	-0.464	Destabilizing	0.979	D	0.723	deleterious	N	0.488006507	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.