TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3323	10192;10193;10194	chr2:178764548;178764547;178764546	chr2:179629275;179629274;179629273
N2AB	3323	10192;10193;10194	chr2:178764548;178764547;178764546	chr2:179629275;179629274;179629273
N2A	3323	10192;10193;10194	chr2:178764548;178764547;178764546	chr2:179629275;179629274;179629273
N2B	3277	10054;10055;10056	chr2:178764548;178764547;178764546	chr2:179629275;179629274;179629273
Novex-1	3277	10054;10055;10056	chr2:178764548;178764547;178764546	chr2:179629275;179629274;179629273
Novex-2	3277	10054;10055;10056	chr2:178764548;178764547;178764546	chr2:179629275;179629274;179629273
Novex-3	3323	10192;10193;10194	chr2:178764548;178764547;178764546	chr2:179629275;179629274;179629273

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-23
• Domain position: 85
• Structural Position: 171
• Q(SASA): 0.3343
• 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
S/A	rs2090015166	None	0.116	N	0.205	0.249	0.239305524855	gnomAD-4.0.0	1.36816E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79859E-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
S/A	0.1029	likely_benign	0.1042	benign	-0.565	Destabilizing	0.116	N	0.205	neutral	N	0.512976332	None	None	N
S/C	0.2743	likely_benign	0.2555	benign	-0.347	Destabilizing	1.0	D	0.572	neutral	None	None	None	None	N
S/D	0.7479	likely_pathogenic	0.6717	pathogenic	0.122	Stabilizing	0.984	D	0.527	neutral	None	None	None	None	N
S/E	0.665	likely_pathogenic	0.6148	pathogenic	0.046	Stabilizing	0.984	D	0.49	neutral	None	None	None	None	N
S/F	0.3801	ambiguous	0.3228	benign	-1.048	Destabilizing	0.999	D	0.657	neutral	None	None	None	None	N
S/G	0.2325	likely_benign	0.2067	benign	-0.711	Destabilizing	0.927	D	0.504	neutral	None	None	None	None	N
S/H	0.5339	ambiguous	0.4839	ambiguous	-1.243	Destabilizing	1.0	D	0.575	neutral	None	None	None	None	N
S/I	0.3916	ambiguous	0.3599	ambiguous	-0.302	Destabilizing	0.991	D	0.667	neutral	None	None	None	None	N
S/K	0.7751	likely_pathogenic	0.6995	pathogenic	-0.518	Destabilizing	0.984	D	0.487	neutral	None	None	None	None	N
S/L	0.2247	likely_benign	0.1981	benign	-0.302	Destabilizing	0.959	D	0.588	neutral	D	0.565018994	None	None	N
S/M	0.3698	ambiguous	0.3157	benign	0.034	Stabilizing	0.999	D	0.589	neutral	None	None	None	None	N
S/N	0.3745	ambiguous	0.3279	benign	-0.258	Destabilizing	0.984	D	0.542	neutral	None	None	None	None	N
S/P	0.8957	likely_pathogenic	0.8429	pathogenic	-0.36	Destabilizing	0.994	D	0.601	neutral	D	0.638389577	None	None	N
S/Q	0.6117	likely_pathogenic	0.5597	ambiguous	-0.534	Destabilizing	0.999	D	0.565	neutral	None	None	None	None	N
S/R	0.636	likely_pathogenic	0.5809	pathogenic	-0.33	Destabilizing	0.995	D	0.601	neutral	None	None	None	None	N
S/T	0.1053	likely_benign	0.0895	benign	-0.388	Destabilizing	0.116	N	0.219	neutral	N	0.494789785	None	None	N
S/V	0.3127	likely_benign	0.2817	benign	-0.36	Destabilizing	0.969	D	0.601	neutral	None	None	None	None	N
S/W	0.6173	likely_pathogenic	0.5538	ambiguous	-0.993	Destabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	N
S/Y	0.3523	ambiguous	0.317	benign	-0.734	Destabilizing	0.999	D	0.654	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.