TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3374	10345;10346;10347	chr2:178759167;178759166;178759165	chr2:179623894;179623893;179623892
N2AB	3374	10345;10346;10347	chr2:178759167;178759166;178759165	chr2:179623894;179623893;179623892
N2A	3374	10345;10346;10347	chr2:178759167;178759166;178759165	chr2:179623894;179623893;179623892
N2B	3328	10207;10208;10209	chr2:178759167;178759166;178759165	chr2:179623894;179623893;179623892
Novex-1	3328	10207;10208;10209	chr2:178759167;178759166;178759165	chr2:179623894;179623893;179623892
Novex-2	3328	10207;10208;10209	chr2:178759167;178759166;178759165	chr2:179623894;179623893;179623892
Novex-3	3374	10345;10346;10347	chr2:178759167;178759166;178759165	chr2:179623894;179623893;179623892

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-24
• Domain position: 30
• Structural Position: 45
• Q(SASA): 0.0889
• 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	rs770029258	-0.77	0.103	N	0.411	0.244	0.276898752692	gnomAD-2.1.1	4E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
K/E	rs770029258	-0.77	0.103	N	0.411	0.244	0.276898752692	gnomAD-4.0.0	6.15742E-06	None	None	None	None	N	None	0	2.23634E-05	None	0	0	None	0	0	7.19488E-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	0.3567	ambiguous	0.2787	benign	-0.015	Destabilizing	0.702	D	0.593	neutral	None	None	None	None	N
K/C	0.8258	likely_pathogenic	0.7538	pathogenic	-0.296	Destabilizing	0.999	D	0.704	prob.neutral	None	None	None	None	N
K/D	0.57	likely_pathogenic	0.4991	ambiguous	0.195	Stabilizing	0.851	D	0.633	neutral	None	None	None	None	N
K/E	0.1653	likely_benign	0.1466	benign	0.196	Stabilizing	0.103	N	0.411	neutral	N	0.503033841	None	None	N
K/F	0.8272	likely_pathogenic	0.7583	pathogenic	-0.28	Destabilizing	0.988	D	0.715	prob.delet.	None	None	None	None	N
K/G	0.6079	likely_pathogenic	0.5124	ambiguous	-0.195	Destabilizing	0.919	D	0.643	neutral	None	None	None	None	N
K/H	0.2923	likely_benign	0.2636	benign	-0.458	Destabilizing	0.999	D	0.625	neutral	None	None	None	None	N
K/I	0.3936	ambiguous	0.3241	benign	0.374	Stabilizing	0.968	D	0.711	prob.delet.	D	0.532260444	None	None	N
K/L	0.3785	ambiguous	0.3101	benign	0.374	Stabilizing	0.851	D	0.643	neutral	None	None	None	None	N
K/M	0.2601	likely_benign	0.2012	benign	0.191	Stabilizing	0.999	D	0.622	neutral	None	None	None	None	N
K/N	0.3755	ambiguous	0.3194	benign	0.207	Stabilizing	0.896	D	0.621	neutral	N	0.511636613	None	None	N
K/P	0.8579	likely_pathogenic	0.7715	pathogenic	0.271	Stabilizing	0.988	D	0.632	neutral	None	None	None	None	N
K/Q	0.1222	likely_benign	0.1133	benign	0.025	Stabilizing	0.968	D	0.604	neutral	N	0.496037553	None	None	N
K/R	0.1042	likely_benign	0.0922	benign	-0.008	Destabilizing	0.059	N	0.391	neutral	N	0.512322306	None	None	N
K/S	0.3851	ambiguous	0.3167	benign	-0.314	Destabilizing	0.851	D	0.579	neutral	None	None	None	None	N
K/T	0.1475	likely_benign	0.1117	benign	-0.167	Destabilizing	0.026	N	0.374	neutral	N	0.488455317	None	None	N
K/V	0.3628	ambiguous	0.3011	benign	0.271	Stabilizing	0.851	D	0.639	neutral	None	None	None	None	N
K/W	0.8393	likely_pathogenic	0.7683	pathogenic	-0.284	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	N
K/Y	0.7213	likely_pathogenic	0.6542	pathogenic	0.082	Stabilizing	0.996	D	0.675	prob.neutral	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.