TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26473	79642;79643;79644	chr2:178566715;178566714;178566713	chr2:179431442;179431441;179431440
N2AB	24832	74719;74720;74721	chr2:178566715;178566714;178566713	chr2:179431442;179431441;179431440
N2A	23905	71938;71939;71940	chr2:178566715;178566714;178566713	chr2:179431442;179431441;179431440
N2B	17408	52447;52448;52449	chr2:178566715;178566714;178566713	chr2:179431442;179431441;179431440
Novex-1	17533	52822;52823;52824	chr2:178566715;178566714;178566713	chr2:179431442;179431441;179431440
Novex-2	17600	53023;53024;53025	chr2:178566715;178566714;178566713	chr2:179431442;179431441;179431440
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-80
• Domain position: 88
• Structural Position: 121
• Q(SASA): 0.1522
• 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
S/G	None	None	0.999	D	0.882	0.686	0.469907520169	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	2.75482E-04	None	0	0	0	0	0
S/N	None	None	0.999	D	0.889	0.538	0.503744809241	gnomAD-4.0.0	6.84346E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99543E-07	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
S/A	0.2216	likely_benign	0.2564	benign	-0.728	Destabilizing	0.998	D	0.848	deleterious	None	None	None	None	N
S/C	0.2542	likely_benign	0.2897	benign	-0.69	Destabilizing	1.0	D	0.871	deleterious	D	0.576603495	None	None	N
S/D	0.9797	likely_pathogenic	0.9747	pathogenic	-0.999	Destabilizing	0.999	D	0.886	deleterious	None	None	None	None	N
S/E	0.9872	likely_pathogenic	0.9844	pathogenic	-0.929	Destabilizing	0.999	D	0.887	deleterious	None	None	None	None	N
S/F	0.8885	likely_pathogenic	0.905	pathogenic	-0.606	Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	N
S/G	0.2523	likely_benign	0.2915	benign	-1.038	Destabilizing	0.999	D	0.882	deleterious	D	0.535582365	None	None	N
S/H	0.9585	likely_pathogenic	0.9593	pathogenic	-1.47	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
S/I	0.7331	likely_pathogenic	0.7633	pathogenic	0.012	Stabilizing	1.0	D	0.894	deleterious	D	0.576096516	None	None	N
S/K	0.997	likely_pathogenic	0.9971	pathogenic	-0.817	Destabilizing	0.999	D	0.881	deleterious	None	None	None	None	N
S/L	0.3917	ambiguous	0.4748	ambiguous	0.012	Stabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
S/M	0.6484	likely_pathogenic	0.6801	pathogenic	0.053	Stabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
S/N	0.851	likely_pathogenic	0.8423	pathogenic	-1.012	Destabilizing	0.999	D	0.889	deleterious	D	0.575843026	None	None	N
S/P	0.9728	likely_pathogenic	0.973	pathogenic	-0.2	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
S/Q	0.9744	likely_pathogenic	0.9721	pathogenic	-1.046	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
S/R	0.9941	likely_pathogenic	0.9945	pathogenic	-0.837	Destabilizing	1.0	D	0.869	deleterious	D	0.552205363	None	None	N
S/T	0.1884	likely_benign	0.2022	benign	-0.86	Destabilizing	0.999	D	0.888	deleterious	D	0.525743316	None	None	N
S/V	0.6093	likely_pathogenic	0.6373	pathogenic	-0.2	Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	N
S/W	0.9644	likely_pathogenic	0.9692	pathogenic	-0.694	Destabilizing	1.0	D	0.912	deleterious	None	None	None	None	N
S/Y	0.9254	likely_pathogenic	0.9276	pathogenic	-0.376	Destabilizing	1.0	D	0.909	deleterious	None	None	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.