TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23974	72145;72146;72147	chr2:178574212;178574211;178574210	chr2:179438939;179438938;179438937
N2AB	22333	67222;67223;67224	chr2:178574212;178574211;178574210	chr2:179438939;179438938;179438937
N2A	21406	64441;64442;64443	chr2:178574212;178574211;178574210	chr2:179438939;179438938;179438937
N2B	14909	44950;44951;44952	chr2:178574212;178574211;178574210	chr2:179438939;179438938;179438937
Novex-1	15034	45325;45326;45327	chr2:178574212;178574211;178574210	chr2:179438939;179438938;179438937
Novex-2	15101	45526;45527;45528	chr2:178574212;178574211;178574210	chr2:179438939;179438938;179438937
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Fn3-62
• Domain position: 51
• Structural Position: 68
• Q(SASA): 0.2638
• Predicted PPI site: I

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
A/G	rs1344955826	-1.164	1.0	N	0.515	0.368	0.266385636622	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.93E-06	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
A/C	0.5353	ambiguous	0.4919	ambiguous	-0.398	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	I
A/D	0.9588	likely_pathogenic	0.9521	pathogenic	-0.825	Destabilizing	1.0	D	0.803	deleterious	N	0.493835954	None	None	I
A/E	0.9308	likely_pathogenic	0.9263	pathogenic	-0.731	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	I
A/F	0.8702	likely_pathogenic	0.8764	pathogenic	-0.468	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
A/G	0.3032	likely_benign	0.3131	benign	-0.929	Destabilizing	1.0	D	0.515	neutral	N	0.480099792	None	None	I
A/H	0.9635	likely_pathogenic	0.9568	pathogenic	-1.243	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
A/I	0.6816	likely_pathogenic	0.681	pathogenic	0.375	Stabilizing	1.0	D	0.793	deleterious	None	None	None	None	I
A/K	0.9872	likely_pathogenic	0.9846	pathogenic	-0.709	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	I
A/L	0.6341	likely_pathogenic	0.6402	pathogenic	0.375	Stabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	I
A/M	0.6542	likely_pathogenic	0.6647	pathogenic	0.275	Stabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
A/N	0.8756	likely_pathogenic	0.8648	pathogenic	-0.68	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
A/P	0.9699	likely_pathogenic	0.9682	pathogenic	0.111	Stabilizing	1.0	D	0.805	deleterious	N	0.489316503	None	None	I
A/Q	0.9267	likely_pathogenic	0.9106	pathogenic	-0.611	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	I
A/R	0.9732	likely_pathogenic	0.9673	pathogenic	-0.709	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
A/S	0.2156	likely_benign	0.1994	benign	-1.121	Destabilizing	1.0	D	0.495	neutral	N	0.469135107	None	None	I
A/T	0.2791	likely_benign	0.2732	benign	-0.902	Destabilizing	1.0	D	0.639	neutral	N	0.473414294	None	None	I
A/V	0.3233	likely_benign	0.3235	benign	0.111	Stabilizing	1.0	D	0.545	neutral	N	0.467438614	None	None	I
A/W	0.9857	likely_pathogenic	0.9837	pathogenic	-1.069	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	I
A/Y	0.9253	likely_pathogenic	0.9222	pathogenic	-0.479	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	I

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.