TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20256	60991;60992;60993	chr2:178590959;178590958;178590957	chr2:179455686;179455685;179455684
N2AB	18615	56068;56069;56070	chr2:178590959;178590958;178590957	chr2:179455686;179455685;179455684
N2A	17688	53287;53288;53289	chr2:178590959;178590958;178590957	chr2:179455686;179455685;179455684
N2B	11191	33796;33797;33798	chr2:178590959;178590958;178590957	chr2:179455686;179455685;179455684
Novex-1	11316	34171;34172;34173	chr2:178590959;178590958;178590957	chr2:179455686;179455685;179455684
Novex-2	11383	34372;34373;34374	chr2:178590959;178590958;178590957	chr2:179455686;179455685;179455684
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-34
• Domain position: 86
• Structural Position: 119
• Q(SASA): 0.3026
• 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
P/L	rs1314557712	None	0.101	N	0.513	0.21	0.490701487448	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
P/L	rs1314557712	None	0.101	N	0.513	0.21	0.490701487448	gnomAD-4.0.0	6.57843E-06	None	None	None	None	N	None	2.41429E-05	0	None	0	0	None	0	0	0	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
P/A	0.0744	likely_benign	0.0815	benign	-1.333	Destabilizing	None	N	0.201	neutral	N	0.432441472	None	None	N
P/C	0.4253	ambiguous	0.4509	ambiguous	-0.779	Destabilizing	0.951	D	0.607	neutral	None	None	None	None	N
P/D	0.2912	likely_benign	0.3374	benign	-1.218	Destabilizing	0.129	N	0.489	neutral	None	None	None	None	N
P/E	0.1735	likely_benign	0.2053	benign	-1.263	Destabilizing	0.004	N	0.227	neutral	None	None	None	None	N
P/F	0.3404	ambiguous	0.3861	ambiguous	-1.088	Destabilizing	0.836	D	0.617	neutral	None	None	None	None	N
P/G	0.2936	likely_benign	0.3214	benign	-1.595	Destabilizing	0.001	N	0.289	neutral	None	None	None	None	N
P/H	0.1677	likely_benign	0.2022	benign	-1.082	Destabilizing	0.921	D	0.619	neutral	N	0.514019918	None	None	N
P/I	0.1928	likely_benign	0.2129	benign	-0.732	Destabilizing	0.418	N	0.691	prob.neutral	None	None	None	None	N
P/K	0.1716	likely_benign	0.203	benign	-1.17	Destabilizing	0.001	N	0.227	neutral	None	None	None	None	N
P/L	0.0859	likely_benign	0.0982	benign	-0.732	Destabilizing	0.101	N	0.513	neutral	N	0.477021755	None	None	N
P/M	0.194	likely_benign	0.2054	benign	-0.517	Destabilizing	0.94	D	0.621	neutral	None	None	None	None	N
P/N	0.2464	likely_benign	0.2737	benign	-0.858	Destabilizing	0.418	N	0.637	neutral	None	None	None	None	N
P/Q	0.1162	likely_benign	0.1342	benign	-1.101	Destabilizing	0.418	N	0.581	neutral	None	None	None	None	N
P/R	0.159	likely_benign	0.1922	benign	-0.544	Destabilizing	0.213	N	0.617	neutral	N	0.476154964	None	None	N
P/S	0.1157	likely_benign	0.1345	benign	-1.295	Destabilizing	0.101	N	0.448	neutral	N	0.47650168	None	None	N
P/T	0.1001	likely_benign	0.1147	benign	-1.246	Destabilizing	0.183	N	0.483	neutral	N	0.490238982	None	None	N
P/V	0.1411	likely_benign	0.1558	benign	-0.898	Destabilizing	0.129	N	0.503	neutral	None	None	None	None	N
P/W	0.5676	likely_pathogenic	0.6303	pathogenic	-1.216	Destabilizing	0.983	D	0.63	neutral	None	None	None	None	N
P/Y	0.3203	likely_benign	0.3657	ambiguous	-0.969	Destabilizing	0.94	D	0.618	neutral	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.