TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33586	100981;100982;100983	chr2:178535991;178535990;178535989	chr2:179400718;179400717;179400716
N2AB	31945	96058;96059;96060	chr2:178535991;178535990;178535989	chr2:179400718;179400717;179400716
N2A	31018	93277;93278;93279	chr2:178535991;178535990;178535989	chr2:179400718;179400717;179400716
N2B	24521	73786;73787;73788	chr2:178535991;178535990;178535989	chr2:179400718;179400717;179400716
Novex-1	24646	74161;74162;74163	chr2:178535991;178535990;178535989	chr2:179400718;179400717;179400716
Novex-2	24713	74362;74363;74364	chr2:178535991;178535990;178535989	chr2:179400718;179400717;179400716
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-158
• Domain position: 91
• Structural Position: 175
• Q(SASA): 0.3863
• 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
E/V	None	None	0.248	N	0.611	0.325	0.407357902709	gnomAD-4.0.0	1.20045E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31264E-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
E/A	0.353	ambiguous	0.3335	benign	-0.713	Destabilizing	0.07	N	0.6	neutral	N	0.476627471	None	None	N
E/C	0.9353	likely_pathogenic	0.9244	pathogenic	-0.2	Destabilizing	0.891	D	0.789	deleterious	None	None	None	None	N
E/D	0.09	likely_benign	0.1073	benign	-0.894	Destabilizing	None	N	0.141	neutral	N	0.450462377	None	None	N
E/F	0.8911	likely_pathogenic	0.8741	pathogenic	-0.553	Destabilizing	0.8	D	0.736	prob.delet.	None	None	None	None	N
E/G	0.5081	ambiguous	0.4848	ambiguous	-1.003	Destabilizing	0.2	N	0.63	neutral	N	0.505123581	None	None	N
E/H	0.7314	likely_pathogenic	0.7029	pathogenic	-0.771	Destabilizing	0.484	N	0.51	neutral	None	None	None	None	N
E/I	0.5853	likely_pathogenic	0.5359	ambiguous	0.052	Stabilizing	0.381	N	0.72	prob.delet.	None	None	None	None	N
E/K	0.6326	likely_pathogenic	0.5291	ambiguous	-0.2	Destabilizing	0.122	N	0.549	neutral	N	0.461407303	None	None	N
E/L	0.6461	likely_pathogenic	0.6047	pathogenic	0.052	Stabilizing	0.233	N	0.683	prob.neutral	None	None	None	None	N
E/M	0.7069	likely_pathogenic	0.6751	pathogenic	0.451	Stabilizing	0.558	D	0.713	prob.delet.	None	None	None	None	N
E/N	0.315	likely_benign	0.3212	benign	-0.549	Destabilizing	0.02	N	0.521	neutral	None	None	None	None	N
E/P	0.9739	likely_pathogenic	0.9762	pathogenic	-0.182	Destabilizing	0.084	N	0.579	neutral	None	None	None	None	N
E/Q	0.3638	ambiguous	0.3187	benign	-0.487	Destabilizing	0.091	N	0.5	neutral	N	0.456540201	None	None	N
E/R	0.7283	likely_pathogenic	0.6447	pathogenic	-0.062	Destabilizing	0.393	N	0.517	neutral	None	None	None	None	N
E/S	0.3409	ambiguous	0.3285	benign	-0.786	Destabilizing	0.048	N	0.534	neutral	None	None	None	None	N
E/T	0.3872	ambiguous	0.3565	ambiguous	-0.55	Destabilizing	0.121	N	0.573	neutral	None	None	None	None	N
E/V	0.3873	ambiguous	0.3577	ambiguous	-0.182	Destabilizing	0.248	N	0.611	neutral	N	0.455214836	None	None	N
E/W	0.9702	likely_pathogenic	0.9649	pathogenic	-0.386	Destabilizing	0.976	D	0.771	deleterious	None	None	None	None	N
E/Y	0.8144	likely_pathogenic	0.7924	pathogenic	-0.308	Destabilizing	0.914	D	0.715	prob.delet.	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.