TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16406	49441;49442;49443	chr2:178614181;178614180;178614179	chr2:179478908;179478907;179478906
N2AB	14765	44518;44519;44520	chr2:178614181;178614180;178614179	chr2:179478908;179478907;179478906
N2A	13838	41737;41738;41739	chr2:178614181;178614180;178614179	chr2:179478908;179478907;179478906
N2B	7341	22246;22247;22248	chr2:178614181;178614180;178614179	chr2:179478908;179478907;179478906
Novex-1	7466	22621;22622;22623	chr2:178614181;178614180;178614179	chr2:179478908;179478907;179478906
Novex-2	7533	22822;22823;22824	chr2:178614181;178614180;178614179	chr2:179478908;179478907;179478906
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-6
• Domain position: 56
• Structural Position: 83
• Q(SASA): 0.8745
• 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
K/R	None	None	0.999	N	0.587	0.284	0.413635276047	gnomAD-4.0.0	1.59385E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86184E-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
K/A	0.6495	likely_pathogenic	0.5764	pathogenic	-0.085	Destabilizing	0.999	D	0.653	neutral	None	None	None	None	N
K/C	0.8712	likely_pathogenic	0.8516	pathogenic	-0.281	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
K/D	0.8931	likely_pathogenic	0.869	pathogenic	0.2	Stabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	N
K/E	0.4645	ambiguous	0.4033	ambiguous	0.223	Stabilizing	0.999	D	0.64	neutral	N	0.477576763	None	None	N
K/F	0.9469	likely_pathogenic	0.9301	pathogenic	-0.226	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	N
K/G	0.7639	likely_pathogenic	0.708	pathogenic	-0.31	Destabilizing	1.0	D	0.604	neutral	None	None	None	None	N
K/H	0.615	likely_pathogenic	0.5779	pathogenic	-0.596	Destabilizing	1.0	D	0.673	neutral	None	None	None	None	N
K/I	0.6795	likely_pathogenic	0.6308	pathogenic	0.434	Stabilizing	1.0	D	0.671	neutral	None	None	None	None	N
K/L	0.6651	likely_pathogenic	0.6124	pathogenic	0.434	Stabilizing	1.0	D	0.604	neutral	None	None	None	None	N
K/M	0.4978	ambiguous	0.4453	ambiguous	0.214	Stabilizing	1.0	D	0.665	neutral	D	0.627475533	None	None	N
K/N	0.7694	likely_pathogenic	0.7257	pathogenic	0.136	Stabilizing	1.0	D	0.733	prob.delet.	N	0.46980147	None	None	N
K/P	0.8472	likely_pathogenic	0.8076	pathogenic	0.29	Stabilizing	1.0	D	0.673	neutral	None	None	None	None	N
K/Q	0.2723	likely_benign	0.2428	benign	-0.011	Destabilizing	1.0	D	0.716	prob.delet.	N	0.475056459	None	None	N
K/R	0.1057	likely_benign	0.1022	benign	-0.112	Destabilizing	0.999	D	0.587	neutral	N	0.474990391	None	None	N
K/S	0.7383	likely_pathogenic	0.6808	pathogenic	-0.405	Destabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	N
K/T	0.3632	ambiguous	0.3091	benign	-0.218	Destabilizing	1.0	D	0.665	neutral	N	0.462479283	None	None	N
K/V	0.6352	likely_pathogenic	0.586	pathogenic	0.29	Stabilizing	1.0	D	0.638	neutral	None	None	None	None	N
K/W	0.9214	likely_pathogenic	0.9054	pathogenic	-0.211	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
K/Y	0.8984	likely_pathogenic	0.8809	pathogenic	0.136	Stabilizing	1.0	D	0.651	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.