TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26585	79978;79979;79980	chr2:178566379;178566378;178566377	chr2:179431106;179431105;179431104
N2AB	24944	75055;75056;75057	chr2:178566379;178566378;178566377	chr2:179431106;179431105;179431104
N2A	24017	72274;72275;72276	chr2:178566379;178566378;178566377	chr2:179431106;179431105;179431104
N2B	17520	52783;52784;52785	chr2:178566379;178566378;178566377	chr2:179431106;179431105;179431104
Novex-1	17645	53158;53159;53160	chr2:178566379;178566378;178566377	chr2:179431106;179431105;179431104
Novex-2	17712	53359;53360;53361	chr2:178566379;178566378;178566377	chr2:179431106;179431105;179431104
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-81
• Domain position: 99
• Structural Position: 132
• Q(SASA): 0.9349
• 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
D/N	rs771202190	None	0.964	N	0.582	0.307	0.390687800842	gnomAD-4.0.0	4.80129E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.25001E-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
D/A	0.5846	likely_pathogenic	0.5632	ambiguous	-0.212	Destabilizing	0.792	D	0.431	neutral	N	0.516455296	None	None	N
D/C	0.9121	likely_pathogenic	0.9079	pathogenic	0.229	Stabilizing	0.998	D	0.785	deleterious	None	None	None	None	N
D/E	0.2009	likely_benign	0.1967	benign	-0.264	Destabilizing	0.049	N	0.359	neutral	N	0.488420546	None	None	N
D/F	0.915	likely_pathogenic	0.9109	pathogenic	-0.404	Destabilizing	0.947	D	0.701	prob.delet.	None	None	None	None	N
D/G	0.6384	likely_pathogenic	0.6198	pathogenic	-0.37	Destabilizing	0.886	D	0.584	neutral	N	0.509330447	None	None	N
D/H	0.8308	likely_pathogenic	0.8297	pathogenic	-0.304	Destabilizing	0.997	D	0.513	neutral	N	0.511865342	None	None	N
D/I	0.7592	likely_pathogenic	0.7471	pathogenic	0.144	Stabilizing	0.078	N	0.579	neutral	None	None	None	None	N
D/K	0.8793	likely_pathogenic	0.8731	pathogenic	0.379	Stabilizing	0.947	D	0.547	neutral	None	None	None	None	N
D/L	0.7715	likely_pathogenic	0.7692	pathogenic	0.144	Stabilizing	0.466	N	0.471	neutral	None	None	None	None	N
D/M	0.8807	likely_pathogenic	0.8803	pathogenic	0.366	Stabilizing	0.985	D	0.685	prob.delet.	None	None	None	None	N
D/N	0.2995	likely_benign	0.2932	benign	0.251	Stabilizing	0.964	D	0.582	neutral	N	0.50619823	None	None	N
D/P	0.936	likely_pathogenic	0.9318	pathogenic	0.047	Stabilizing	0.991	D	0.557	neutral	None	None	None	None	N
D/Q	0.7767	likely_pathogenic	0.7716	pathogenic	0.248	Stabilizing	0.947	D	0.587	neutral	None	None	None	None	N
D/R	0.9126	likely_pathogenic	0.9085	pathogenic	0.424	Stabilizing	0.947	D	0.639	neutral	None	None	None	None	N
D/S	0.5437	ambiguous	0.5261	ambiguous	0.137	Stabilizing	0.835	D	0.613	neutral	None	None	None	None	N
D/T	0.7403	likely_pathogenic	0.7241	pathogenic	0.252	Stabilizing	0.947	D	0.554	neutral	None	None	None	None	N
D/V	0.5622	ambiguous	0.539	ambiguous	0.047	Stabilizing	0.397	N	0.493	neutral	N	0.500509036	None	None	N
D/W	0.9795	likely_pathogenic	0.9787	pathogenic	-0.36	Destabilizing	0.998	D	0.792	deleterious	None	None	None	None	N
D/Y	0.6018	likely_pathogenic	0.5944	pathogenic	-0.192	Destabilizing	0.964	D	0.655	prob.neutral	N	0.512118831	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.