TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33728	101407;101408;101409	chr2:178535433;178535432;178535431	chr2:179400160;179400159;179400158
N2AB	32087	96484;96485;96486	chr2:178535433;178535432;178535431	chr2:179400160;179400159;179400158
N2A	31160	93703;93704;93705	chr2:178535433;178535432;178535431	chr2:179400160;179400159;179400158
N2B	24663	74212;74213;74214	chr2:178535433;178535432;178535431	chr2:179400160;179400159;179400158
Novex-1	24788	74587;74588;74589	chr2:178535433;178535432;178535431	chr2:179400160;179400159;179400158
Novex-2	24855	74788;74789;74790	chr2:178535433;178535432;178535431	chr2:179400160;179400159;179400158
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: Fn3-132
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.2468
• 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/N	None	None	1.0	N	0.822	0.438	0.199424873507	gnomAD-4.0.0	1.59125E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43275E-05	0
K/T	None	None	1.0	N	0.817	0.521	0.471456661759	gnomAD-4.0.0	1.59115E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85794E-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	0.9649	likely_pathogenic	0.9474	pathogenic	-1.341	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
K/C	0.9479	likely_pathogenic	0.9196	pathogenic	-1.329	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
K/D	0.9973	likely_pathogenic	0.9969	pathogenic	-2.21	Highly Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
K/E	0.9772	likely_pathogenic	0.9606	pathogenic	-1.878	Destabilizing	0.999	D	0.732	prob.delet.	N	0.505286343	None	None	N
K/F	0.9881	likely_pathogenic	0.9758	pathogenic	-0.613	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
K/G	0.9788	likely_pathogenic	0.9711	pathogenic	-1.829	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
K/H	0.9116	likely_pathogenic	0.8691	pathogenic	-1.541	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
K/I	0.9319	likely_pathogenic	0.882	pathogenic	0.066	Stabilizing	0.999	D	0.879	deleterious	N	0.518729518	None	None	N
K/L	0.9211	likely_pathogenic	0.8515	pathogenic	0.066	Stabilizing	0.999	D	0.807	deleterious	None	None	None	None	N
K/M	0.7891	likely_pathogenic	0.6522	pathogenic	-0.363	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
K/N	0.9879	likely_pathogenic	0.9829	pathogenic	-1.866	Destabilizing	1.0	D	0.822	deleterious	N	0.493930038	None	None	N
K/P	0.9992	likely_pathogenic	0.9992	pathogenic	-0.386	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
K/Q	0.8401	likely_pathogenic	0.7114	pathogenic	-1.429	Destabilizing	1.0	D	0.824	deleterious	N	0.480598723	None	None	N
K/R	0.3189	likely_benign	0.235	benign	-0.754	Destabilizing	0.999	D	0.726	prob.delet.	N	0.46582054	None	None	N
K/S	0.9859	likely_pathogenic	0.978	pathogenic	-2.303	Highly Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
K/T	0.9342	likely_pathogenic	0.9051	pathogenic	-1.71	Destabilizing	1.0	D	0.817	deleterious	N	0.46797497	None	None	N
K/V	0.9007	likely_pathogenic	0.8464	pathogenic	-0.386	Destabilizing	0.999	D	0.831	deleterious	None	None	None	None	N
K/W	0.9916	likely_pathogenic	0.985	pathogenic	-0.732	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
K/Y	0.9374	likely_pathogenic	0.9	pathogenic	-0.36	Destabilizing	1.0	D	0.867	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.