TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33750	101473;101474;101475	chr2:178535367;178535366;178535365	chr2:179400094;179400093;179400092
N2AB	32109	96550;96551;96552	chr2:178535367;178535366;178535365	chr2:179400094;179400093;179400092
N2A	31182	93769;93770;93771	chr2:178535367;178535366;178535365	chr2:179400094;179400093;179400092
N2B	24685	74278;74279;74280	chr2:178535367;178535366;178535365	chr2:179400094;179400093;179400092
Novex-1	24810	74653;74654;74655	chr2:178535367;178535366;178535365	chr2:179400094;179400093;179400092
Novex-2	24877	74854;74855;74856	chr2:178535367;178535366;178535365	chr2:179400094;179400093;179400092
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-132
• Domain position: 62
• Structural Position: 94
• Q(SASA): 0.4964
• 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
I/F	rs1690954165	None	0.9	N	0.503	0.172	None	gnomAD-4.0.0	6.3642E-06	None	None	None	None	N	None	0	0	None	0	0	None	7.53296E-05	0	0	0	0
I/T	None	None	0.659	N	0.489	0.346	0.522717468363	gnomAD-4.0.0	1.36834E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79884E-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
I/A	0.5622	ambiguous	0.476	ambiguous	-1.177	Destabilizing	0.638	D	0.465	neutral	None	None	None	None	N
I/C	0.7246	likely_pathogenic	0.7312	pathogenic	-0.794	Destabilizing	0.996	D	0.641	neutral	None	None	None	None	N
I/D	0.9012	likely_pathogenic	0.8755	pathogenic	-0.282	Destabilizing	0.995	D	0.715	prob.delet.	None	None	None	None	N
I/E	0.8254	likely_pathogenic	0.7623	pathogenic	-0.325	Destabilizing	0.978	D	0.677	prob.neutral	None	None	None	None	N
I/F	0.3526	ambiguous	0.3042	benign	-0.894	Destabilizing	0.9	D	0.503	neutral	N	0.455430188	None	None	N
I/G	0.7945	likely_pathogenic	0.7477	pathogenic	-1.431	Destabilizing	0.984	D	0.658	neutral	None	None	None	None	N
I/H	0.7922	likely_pathogenic	0.7614	pathogenic	-0.562	Destabilizing	0.997	D	0.713	prob.delet.	None	None	None	None	N
I/K	0.7019	likely_pathogenic	0.6055	pathogenic	-0.656	Destabilizing	0.641	D	0.687	prob.neutral	None	None	None	None	N
I/L	0.2098	likely_benign	0.1883	benign	-0.592	Destabilizing	0.017	N	0.253	neutral	N	0.42903302	None	None	N
I/M	0.1578	likely_benign	0.1451	benign	-0.5	Destabilizing	0.73	D	0.567	neutral	N	0.497450169	None	None	N
I/N	0.5208	ambiguous	0.4436	ambiguous	-0.439	Destabilizing	0.993	D	0.725	prob.delet.	N	0.454043321	None	None	N
I/P	0.846	likely_pathogenic	0.8312	pathogenic	-0.754	Destabilizing	0.995	D	0.717	prob.delet.	None	None	None	None	N
I/Q	0.6855	likely_pathogenic	0.6184	pathogenic	-0.634	Destabilizing	0.987	D	0.729	prob.delet.	None	None	None	None	N
I/R	0.6168	likely_pathogenic	0.5342	ambiguous	-0.069	Destabilizing	0.96	D	0.726	prob.delet.	None	None	None	None	N
I/S	0.4981	ambiguous	0.4458	ambiguous	-1.051	Destabilizing	0.958	D	0.635	neutral	N	0.413138061	None	None	N
I/T	0.3358	likely_benign	0.2405	benign	-0.973	Destabilizing	0.659	D	0.489	neutral	N	0.401688916	None	None	N
I/V	0.1059	likely_benign	0.0743	benign	-0.754	Destabilizing	None	N	0.153	neutral	N	0.433457405	None	None	N
I/W	0.8661	likely_pathogenic	0.8969	pathogenic	-0.886	Destabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	N
I/Y	0.7041	likely_pathogenic	0.7361	pathogenic	-0.665	Destabilizing	0.739	D	0.664	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.