TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16445	49558;49559;49560	chr2:178614064;178614063;178614062	chr2:179478791;179478790;179478789
N2AB	14804	44635;44636;44637	chr2:178614064;178614063;178614062	chr2:179478791;179478790;179478789
N2A	13877	41854;41855;41856	chr2:178614064;178614063;178614062	chr2:179478791;179478790;179478789
N2B	7380	22363;22364;22365	chr2:178614064;178614063;178614062	chr2:179478791;179478790;179478789
Novex-1	7505	22738;22739;22740	chr2:178614064;178614063;178614062	chr2:179478791;179478790;179478789
Novex-2	7572	22939;22940;22941	chr2:178614064;178614063;178614062	chr2:179478791;179478790;179478789
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: Fn3-6
• Domain position: 95
• Structural Position: 131
• Q(SASA): 0.3013
• 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/E	rs1553701901	None	0.919	N	0.393	0.171	0.272205846399	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
K/E	rs1553701901	None	0.919	N	0.393	0.171	0.272205846399	gnomAD-4.0.0	2.56791E-06	None	None	None	None	N	None	3.38719E-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
K/A	0.4975	ambiguous	0.4559	ambiguous	-0.349	Destabilizing	0.938	D	0.455	neutral	None	None	None	None	N
K/C	0.6093	likely_pathogenic	0.6266	pathogenic	-0.302	Destabilizing	0.999	D	0.829	deleterious	None	None	None	None	N
K/D	0.8405	likely_pathogenic	0.7897	pathogenic	0.045	Stabilizing	0.991	D	0.502	neutral	None	None	None	None	N
K/E	0.3415	ambiguous	0.3202	benign	0.102	Stabilizing	0.919	D	0.393	neutral	N	0.462051366	None	None	N
K/F	0.8715	likely_pathogenic	0.8569	pathogenic	-0.288	Destabilizing	0.997	D	0.766	deleterious	None	None	None	None	N
K/G	0.6692	likely_pathogenic	0.6138	pathogenic	-0.656	Destabilizing	0.968	D	0.617	neutral	None	None	None	None	N
K/H	0.3725	ambiguous	0.3529	ambiguous	-1.089	Destabilizing	0.997	D	0.477	neutral	None	None	None	None	N
K/I	0.4872	ambiguous	0.4662	ambiguous	0.413	Stabilizing	0.996	D	0.782	deleterious	N	0.520271798	None	None	N
K/L	0.5634	ambiguous	0.5266	ambiguous	0.413	Stabilizing	0.938	D	0.617	neutral	None	None	None	None	N
K/M	0.3667	ambiguous	0.3491	ambiguous	0.393	Stabilizing	0.999	D	0.48	neutral	None	None	None	None	N
K/N	0.6351	likely_pathogenic	0.5846	pathogenic	-0.067	Destabilizing	0.958	D	0.476	neutral	D	0.627904882	None	None	N
K/P	0.9812	likely_pathogenic	0.9642	pathogenic	0.19	Stabilizing	0.997	D	0.537	neutral	None	None	None	None	N
K/Q	0.1542	likely_benign	0.1522	benign	-0.238	Destabilizing	0.919	D	0.506	neutral	N	0.466554061	None	None	N
K/R	0.0786	likely_benign	0.0793	benign	-0.382	Destabilizing	0.015	N	0.13	neutral	N	0.45640191	None	None	N
K/S	0.5476	ambiguous	0.5165	ambiguous	-0.695	Destabilizing	0.968	D	0.392	neutral	None	None	None	None	N
K/T	0.2594	likely_benign	0.2434	benign	-0.452	Destabilizing	0.958	D	0.531	neutral	N	0.466095885	None	None	N
K/V	0.4002	ambiguous	0.3825	ambiguous	0.19	Stabilizing	0.991	D	0.595	neutral	None	None	None	None	N
K/W	0.8699	likely_pathogenic	0.8472	pathogenic	-0.18	Destabilizing	0.999	D	0.781	deleterious	None	None	None	None	N
K/Y	0.7738	likely_pathogenic	0.749	pathogenic	0.134	Stabilizing	0.997	D	0.785	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.