TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19028	57307;57308;57309	chr2:178598535;178598534;178598533	chr2:179463262;179463261;179463260
N2AB	17387	52384;52385;52386	chr2:178598535;178598534;178598533	chr2:179463262;179463261;179463260
N2A	16460	49603;49604;49605	chr2:178598535;178598534;178598533	chr2:179463262;179463261;179463260
N2B	9963	30112;30113;30114	chr2:178598535;178598534;178598533	chr2:179463262;179463261;179463260
Novex-1	10088	30487;30488;30489	chr2:178598535;178598534;178598533	chr2:179463262;179463261;179463260
Novex-2	10155	30688;30689;30690	chr2:178598535;178598534;178598533	chr2:179463262;179463261;179463260
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-26
• Domain position: 41
• Structural Position: 43
• Q(SASA): 0.1026
• 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/T	rs765612779	-1.94	0.999	N	0.73	0.476	0.359763055319	gnomAD-2.1.1	8.18E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.79E-05	0
K/T	rs765612779	-1.94	0.999	N	0.73	0.476	0.359763055319	gnomAD-4.0.0	3.20645E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.73414E-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	0.5186	ambiguous	0.5777	pathogenic	-1.884	Destabilizing	0.998	D	0.517	neutral	None	None	None	None	N
K/C	0.4404	ambiguous	0.4801	ambiguous	-1.736	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
K/D	0.9674	likely_pathogenic	0.9769	pathogenic	-2.164	Highly Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
K/E	0.3861	ambiguous	0.4352	ambiguous	-1.875	Destabilizing	0.996	D	0.423	neutral	N	0.508091237	None	None	N
K/F	0.8815	likely_pathogenic	0.9095	pathogenic	-0.941	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
K/G	0.7506	likely_pathogenic	0.7929	pathogenic	-2.298	Highly Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
K/H	0.5817	likely_pathogenic	0.6222	pathogenic	-2.287	Highly Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
K/I	0.5614	ambiguous	0.6143	pathogenic	-0.688	Destabilizing	1.0	D	0.886	deleterious	N	0.474966863	None	None	N
K/L	0.4089	ambiguous	0.4486	ambiguous	-0.688	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
K/M	0.2117	likely_benign	0.2268	benign	-1.185	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
K/N	0.8818	likely_pathogenic	0.907	pathogenic	-2.002	Highly Destabilizing	0.999	D	0.668	neutral	N	0.474966863	None	None	N
K/P	0.9902	likely_pathogenic	0.9934	pathogenic	-1.073	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
K/Q	0.1053	likely_benign	0.1146	benign	-1.583	Destabilizing	0.999	D	0.645	neutral	N	0.459451928	None	None	N
K/R	0.0723	likely_benign	0.0734	benign	-1.546	Destabilizing	0.64	D	0.287	neutral	N	0.4010197	None	None	N
K/S	0.7382	likely_pathogenic	0.7939	pathogenic	-2.452	Highly Destabilizing	0.998	D	0.501	neutral	None	None	None	None	N
K/T	0.4191	ambiguous	0.4477	ambiguous	-1.952	Destabilizing	0.999	D	0.73	prob.delet.	N	0.469940434	None	None	N
K/V	0.4552	ambiguous	0.5031	ambiguous	-1.073	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
K/W	0.8802	likely_pathogenic	0.8997	pathogenic	-1.084	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
K/Y	0.8286	likely_pathogenic	0.852	pathogenic	-0.805	Destabilizing	1.0	D	0.882	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.