TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32661	98206;98207;98208	chr2:178540185;178540184;178540183	chr2:179404912;179404911;179404910
N2AB	31020	93283;93284;93285	chr2:178540185;178540184;178540183	chr2:179404912;179404911;179404910
N2A	30093	90502;90503;90504	chr2:178540185;178540184;178540183	chr2:179404912;179404911;179404910
N2B	23596	71011;71012;71013	chr2:178540185;178540184;178540183	chr2:179404912;179404911;179404910
Novex-1	23721	71386;71387;71388	chr2:178540185;178540184;178540183	chr2:179404912;179404911;179404910
Novex-2	23788	71587;71588;71589	chr2:178540185;178540184;178540183	chr2:179404912;179404911;179404910
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-126
• Domain position: 62
• Structural Position: 92
• Q(SASA): 0.3302
• 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
T/I	rs1427043562	None	1.0	N	0.836	0.429	0.60179161069	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/I	rs1427043562	None	1.0	N	0.836	0.429	0.60179161069	gnomAD-4.0.0	6.57324E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47016E-05	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
T/A	0.3163	likely_benign	0.317	benign	-0.77	Destabilizing	0.999	D	0.557	neutral	N	0.492038069	None	None	N
T/C	0.6862	likely_pathogenic	0.6665	pathogenic	-0.438	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
T/D	0.8874	likely_pathogenic	0.8884	pathogenic	0.479	Stabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
T/E	0.7859	likely_pathogenic	0.8032	pathogenic	0.452	Stabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
T/F	0.7222	likely_pathogenic	0.6879	pathogenic	-1.113	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
T/G	0.786	likely_pathogenic	0.7574	pathogenic	-0.96	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
T/H	0.6356	likely_pathogenic	0.6213	pathogenic	-1.194	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
T/I	0.3564	ambiguous	0.3333	benign	-0.372	Destabilizing	1.0	D	0.836	deleterious	N	0.502064475	None	None	N
T/K	0.6388	likely_pathogenic	0.6324	pathogenic	-0.376	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
T/L	0.2659	likely_benign	0.2497	benign	-0.372	Destabilizing	0.999	D	0.692	prob.neutral	None	None	None	None	N
T/M	0.2036	likely_benign	0.206	benign	-0.169	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
T/N	0.4863	ambiguous	0.4793	ambiguous	-0.263	Destabilizing	1.0	D	0.732	prob.delet.	N	0.485935229	None	None	N
T/P	0.6982	likely_pathogenic	0.664	pathogenic	-0.475	Destabilizing	1.0	D	0.842	deleterious	N	0.487456167	None	None	N
T/Q	0.5501	ambiguous	0.5472	ambiguous	-0.408	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
T/R	0.5679	likely_pathogenic	0.5537	ambiguous	-0.187	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
T/S	0.3829	ambiguous	0.3682	ambiguous	-0.611	Destabilizing	0.999	D	0.526	neutral	N	0.486593566	None	None	N
T/V	0.2182	likely_benign	0.2115	benign	-0.475	Destabilizing	0.999	D	0.594	neutral	None	None	None	None	N
T/W	0.9294	likely_pathogenic	0.9282	pathogenic	-1.038	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
T/Y	0.7623	likely_pathogenic	0.7426	pathogenic	-0.78	Destabilizing	1.0	D	0.867	deleterious	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.