TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33450	100573;100574;100575	chr2:178536399;178536398;178536397	chr2:179401126;179401125;179401124
N2AB	31809	95650;95651;95652	chr2:178536399;178536398;178536397	chr2:179401126;179401125;179401124
N2A	30882	92869;92870;92871	chr2:178536399;178536398;178536397	chr2:179401126;179401125;179401124
N2B	24385	73378;73379;73380	chr2:178536399;178536398;178536397	chr2:179401126;179401125;179401124
Novex-1	24510	73753;73754;73755	chr2:178536399;178536398;178536397	chr2:179401126;179401125;179401124
Novex-2	24577	73954;73955;73956	chr2:178536399;178536398;178536397	chr2:179401126;179401125;179401124
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-131
• Domain position: 59
• Structural Position: 89
• Q(SASA): 0.0769
• 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
T/N	rs1691516796	None	1.0	N	0.751	0.39	0.457377140028	gnomAD-4.0.0	1.36857E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.799E-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
T/A	0.2561	likely_benign	0.2803	benign	-0.712	Destabilizing	0.999	D	0.667	neutral	N	0.485348891	None	None	N
T/C	0.7293	likely_pathogenic	0.7133	pathogenic	-0.469	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
T/D	0.8102	likely_pathogenic	0.8401	pathogenic	-0.507	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
T/E	0.7344	likely_pathogenic	0.7901	pathogenic	-0.363	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
T/F	0.8402	likely_pathogenic	0.8795	pathogenic	-0.605	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
T/G	0.6084	likely_pathogenic	0.6072	pathogenic	-1.068	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
T/H	0.7229	likely_pathogenic	0.762	pathogenic	-1.102	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
T/I	0.6805	likely_pathogenic	0.734	pathogenic	0.19	Stabilizing	1.0	D	0.759	deleterious	N	0.510138643	None	None	N
T/K	0.5849	likely_pathogenic	0.6658	pathogenic	-0.3	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
T/L	0.3227	likely_benign	0.3283	benign	0.19	Stabilizing	0.999	D	0.734	prob.delet.	None	None	None	None	N
T/M	0.2035	likely_benign	0.2023	benign	0.021	Stabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
T/N	0.2291	likely_benign	0.2446	benign	-0.788	Destabilizing	1.0	D	0.751	deleterious	N	0.506899158	None	None	N
T/P	0.2962	likely_benign	0.3406	ambiguous	-0.079	Destabilizing	1.0	D	0.758	deleterious	N	0.480651629	None	None	N
T/Q	0.5818	likely_pathogenic	0.6202	pathogenic	-0.627	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
T/R	0.5124	ambiguous	0.5916	pathogenic	-0.358	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
T/S	0.3155	likely_benign	0.333	benign	-1.068	Destabilizing	0.999	D	0.66	neutral	N	0.490006472	None	None	N
T/V	0.5253	ambiguous	0.5539	ambiguous	-0.079	Destabilizing	0.999	D	0.706	prob.neutral	None	None	None	None	N
T/W	0.9529	likely_pathogenic	0.9625	pathogenic	-0.752	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
T/Y	0.781	likely_pathogenic	0.8268	pathogenic	-0.354	Destabilizing	1.0	D	0.791	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.