TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16519	49780;49781;49782	chr2:178613254;178613253;178613252	chr2:179477981;179477980;179477979
N2AB	14878	44857;44858;44859	chr2:178613254;178613253;178613252	chr2:179477981;179477980;179477979
N2A	13951	42076;42077;42078	chr2:178613254;178613253;178613252	chr2:179477981;179477980;179477979
N2B	7454	22585;22586;22587	chr2:178613254;178613253;178613252	chr2:179477981;179477980;179477979
Novex-1	7579	22960;22961;22962	chr2:178613254;178613253;178613252	chr2:179477981;179477980;179477979
Novex-2	7646	23161;23162;23163	chr2:178613254;178613253;178613252	chr2:179477981;179477980;179477979
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: Fn3-7
• Domain position: 70
• Structural Position: 102
• Q(SASA): 0.3338
• 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/E	None	None	0.996	N	0.429	0.397	0.313518423057	gnomAD-4.0.0	2.7424E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.60142E-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	0.9002	likely_pathogenic	0.8127	pathogenic	-0.719	Destabilizing	0.998	D	0.547	neutral	None	None	None	None	N
K/C	0.9491	likely_pathogenic	0.8573	pathogenic	-0.704	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
K/D	0.9664	likely_pathogenic	0.9237	pathogenic	-0.21	Destabilizing	0.998	D	0.567	neutral	None	None	None	None	N
K/E	0.7688	likely_pathogenic	0.6036	pathogenic	-0.041	Destabilizing	0.996	D	0.429	neutral	N	0.452270374	None	None	N
K/F	0.9853	likely_pathogenic	0.9668	pathogenic	-0.206	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
K/G	0.904	likely_pathogenic	0.8315	pathogenic	-1.12	Destabilizing	0.997	D	0.579	neutral	None	None	None	None	N
K/H	0.7221	likely_pathogenic	0.5791	pathogenic	-1.188	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	N
K/I	0.8882	likely_pathogenic	0.7876	pathogenic	0.347	Stabilizing	1.0	D	0.751	deleterious	N	0.482744525	None	None	N
K/L	0.8466	likely_pathogenic	0.7414	pathogenic	0.347	Stabilizing	1.0	D	0.635	neutral	None	None	None	None	N
K/M	0.7249	likely_pathogenic	0.5722	pathogenic	0.008	Stabilizing	1.0	D	0.651	neutral	None	None	None	None	N
K/N	0.8946	likely_pathogenic	0.8015	pathogenic	-0.713	Destabilizing	0.884	D	0.255	neutral	N	0.468212	None	None	N
K/P	0.9941	likely_pathogenic	0.9887	pathogenic	0.021	Stabilizing	1.0	D	0.653	neutral	None	None	None	None	N
K/Q	0.3882	ambiguous	0.2621	benign	-0.616	Destabilizing	0.999	D	0.641	neutral	N	0.459507418	None	None	N
K/R	0.1346	likely_benign	0.1155	benign	-0.58	Destabilizing	0.998	D	0.514	neutral	N	0.460414354	None	None	N
K/S	0.9214	likely_pathogenic	0.8477	pathogenic	-1.347	Destabilizing	0.997	D	0.458	neutral	None	None	None	None	N
K/T	0.7293	likely_pathogenic	0.5843	pathogenic	-0.952	Destabilizing	0.999	D	0.616	neutral	N	0.440200392	None	None	N
K/V	0.8376	likely_pathogenic	0.723	pathogenic	0.021	Stabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
K/W	0.9787	likely_pathogenic	0.9496	pathogenic	-0.129	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
K/Y	0.9459	likely_pathogenic	0.8868	pathogenic	0.146	Stabilizing	1.0	D	0.721	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.