TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21798	65617;65618;65619	chr2:178583790;178583789;178583788	chr2:179448517;179448516;179448515
N2AB	20157	60694;60695;60696	chr2:178583790;178583789;178583788	chr2:179448517;179448516;179448515
N2A	19230	57913;57914;57915	chr2:178583790;178583789;178583788	chr2:179448517;179448516;179448515
N2B	12733	38422;38423;38424	chr2:178583790;178583789;178583788	chr2:179448517;179448516;179448515
Novex-1	12858	38797;38798;38799	chr2:178583790;178583789;178583788	chr2:179448517;179448516;179448515
Novex-2	12925	38998;38999;39000	chr2:178583790;178583789;178583788	chr2:179448517;179448516;179448515
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: Fn3-46
• Domain position: 42
• Structural Position: 44
• Q(SASA): 0.3663
• 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/T	rs776173264	-0.616	1.0	N	0.727	0.464	0.483521307902	gnomAD-2.1.1	4.11E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.1E-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
K/A	0.5512	ambiguous	0.4357	ambiguous	-0.598	Destabilizing	0.999	D	0.667	neutral	None	None	None	None	N
K/C	0.7015	likely_pathogenic	0.6312	pathogenic	-0.541	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
K/D	0.8884	likely_pathogenic	0.8036	pathogenic	-0.038	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
K/E	0.3719	ambiguous	0.2659	benign	0.092	Stabilizing	0.999	D	0.565	neutral	N	0.4439624	None	None	N
K/F	0.8575	likely_pathogenic	0.7947	pathogenic	-0.217	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
K/G	0.7542	likely_pathogenic	0.665	pathogenic	-0.963	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
K/H	0.4397	ambiguous	0.3639	ambiguous	-1.127	Destabilizing	1.0	D	0.66	neutral	None	None	None	None	N
K/I	0.4879	ambiguous	0.3767	ambiguous	0.353	Stabilizing	1.0	D	0.772	deleterious	N	0.474473111	None	None	N
K/L	0.3881	ambiguous	0.3123	benign	0.353	Stabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
K/M	0.3611	ambiguous	0.279	benign	0.051	Stabilizing	1.0	D	0.653	neutral	None	None	None	None	N
K/N	0.7269	likely_pathogenic	0.6149	pathogenic	-0.428	Destabilizing	1.0	D	0.66	neutral	N	0.520655102	None	None	N
K/P	0.6034	likely_pathogenic	0.5031	ambiguous	0.066	Stabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
K/Q	0.1828	likely_benign	0.1419	benign	-0.407	Destabilizing	1.0	D	0.644	neutral	N	0.512707623	None	None	N
K/R	0.0816	likely_benign	0.0764	benign	-0.474	Destabilizing	0.999	D	0.529	neutral	N	0.467572766	None	None	N
K/S	0.6942	likely_pathogenic	0.5832	pathogenic	-1.051	Destabilizing	0.999	D	0.598	neutral	None	None	None	None	N
K/T	0.4171	ambiguous	0.3134	benign	-0.709	Destabilizing	1.0	D	0.727	prob.delet.	N	0.500645189	None	None	N
K/V	0.4265	ambiguous	0.3346	benign	0.066	Stabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
K/W	0.8565	likely_pathogenic	0.8109	pathogenic	-0.13	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
K/Y	0.7614	likely_pathogenic	0.6841	pathogenic	0.14	Stabilizing	1.0	D	0.722	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.