TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33772	101539;101540;101541	chr2:178535301;178535300;178535299	chr2:179400028;179400027;179400026
N2AB	32131	96616;96617;96618	chr2:178535301;178535300;178535299	chr2:179400028;179400027;179400026
N2A	31204	93835;93836;93837	chr2:178535301;178535300;178535299	chr2:179400028;179400027;179400026
N2B	24707	74344;74345;74346	chr2:178535301;178535300;178535299	chr2:179400028;179400027;179400026
Novex-1	24832	74719;74720;74721	chr2:178535301;178535300;178535299	chr2:179400028;179400027;179400026
Novex-2	24899	74920;74921;74922	chr2:178535301;178535300;178535299	chr2:179400028;179400027;179400026
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: Fn3-132
• Domain position: 84
• Structural Position: 119
• Q(SASA): 0.794
• 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	rs1362410602	None	0.028	N	0.409	0.151	0.193865811164	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/E	rs1362410602	None	0.028	N	0.409	0.151	0.193865811164	gnomAD-4.0.0	2.56176E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.39262E-06	1.33994E-05	0
K/N	rs1255240121	None	0.315	N	0.459	0.107	0.156986980423	gnomAD-4.0.0	3.18225E-06	None	None	None	None	N	None	0	0	None	0	5.54508E-05	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	0.2445	likely_benign	0.2464	benign	0.053	Stabilizing	0.112	N	0.397	neutral	None	None	None	None	N
K/C	0.7453	likely_pathogenic	0.7508	pathogenic	-0.228	Destabilizing	0.98	D	0.449	neutral	None	None	None	None	N
K/D	0.458	ambiguous	0.4802	ambiguous	-0.024	Destabilizing	0.379	N	0.519	neutral	None	None	None	None	N
K/E	0.1555	likely_benign	0.146	benign	-0.011	Destabilizing	0.028	N	0.409	neutral	N	0.355516697	None	None	N
K/F	0.7546	likely_pathogenic	0.787	pathogenic	-0.138	Destabilizing	0.633	D	0.473	neutral	None	None	None	None	N
K/G	0.3436	ambiguous	0.4065	ambiguous	-0.144	Destabilizing	0.001	N	0.224	neutral	None	None	None	None	N
K/H	0.3819	ambiguous	0.3766	ambiguous	-0.35	Destabilizing	0.47	N	0.509	neutral	None	None	None	None	N
K/I	0.3499	ambiguous	0.3676	ambiguous	0.495	Stabilizing	0.009	N	0.565	neutral	None	None	None	None	N
K/L	0.2964	likely_benign	0.298	benign	0.495	Stabilizing	0.004	N	0.498	neutral	None	None	None	None	N
K/M	0.2601	likely_benign	0.2619	benign	0.142	Stabilizing	0.281	N	0.507	neutral	N	0.484734374	None	None	N
K/N	0.3247	likely_benign	0.3564	ambiguous	0.182	Stabilizing	0.315	N	0.459	neutral	N	0.469303562	None	None	N
K/P	0.4148	ambiguous	0.4295	ambiguous	0.375	Stabilizing	0.002	N	0.243	neutral	None	None	None	None	N
K/Q	0.1322	likely_benign	0.125	benign	0.051	Stabilizing	0.001	N	0.143	neutral	N	0.417970665	None	None	N
K/R	0.1031	likely_benign	0.0982	benign	-0.043	Destabilizing	0.041	N	0.488	neutral	N	0.433324119	None	None	N
K/S	0.3158	likely_benign	0.3324	benign	-0.248	Destabilizing	0.023	N	0.186	neutral	None	None	None	None	N
K/T	0.1855	likely_benign	0.1816	benign	-0.089	Destabilizing	0.065	N	0.481	neutral	N	0.454584826	None	None	N
K/V	0.3062	likely_benign	0.3096	benign	0.375	Stabilizing	None	N	0.333	neutral	None	None	None	None	N
K/W	0.8436	likely_pathogenic	0.8585	pathogenic	-0.197	Destabilizing	0.987	D	0.491	neutral	None	None	None	None	N
K/Y	0.6515	likely_pathogenic	0.6945	pathogenic	0.157	Stabilizing	0.168	N	0.486	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.