TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22068	66427;66428;66429	chr2:178582167;178582166;178582165	chr2:179446894;179446893;179446892
N2AB	20427	61504;61505;61506	chr2:178582167;178582166;178582165	chr2:179446894;179446893;179446892
N2A	19500	58723;58724;58725	chr2:178582167;178582166;178582165	chr2:179446894;179446893;179446892
N2B	13003	39232;39233;39234	chr2:178582167;178582166;178582165	chr2:179446894;179446893;179446892
Novex-1	13128	39607;39608;39609	chr2:178582167;178582166;178582165	chr2:179446894;179446893;179446892
Novex-2	13195	39808;39809;39810	chr2:178582167;178582166;178582165	chr2:179446894;179446893;179446892
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-48
• Domain position: 14
• Structural Position: 16
• Q(SASA): 0.1991
• 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	None	None	0.642	N	0.509	0.354	0.4018988957	gnomAD-4.0.0	1.59372E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86049E-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
T/A	0.2878	likely_benign	0.3093	benign	-0.541	Destabilizing	0.174	N	0.458	neutral	N	0.50788338	None	None	N
T/C	0.7217	likely_pathogenic	0.7201	pathogenic	-0.465	Destabilizing	0.991	D	0.509	neutral	None	None	None	None	N
T/D	0.8551	likely_pathogenic	0.8309	pathogenic	-1.697	Destabilizing	0.404	N	0.493	neutral	None	None	None	None	N
T/E	0.8519	likely_pathogenic	0.8337	pathogenic	-1.609	Destabilizing	0.575	D	0.495	neutral	None	None	None	None	N
T/F	0.8173	likely_pathogenic	0.8034	pathogenic	-0.34	Destabilizing	0.826	D	0.562	neutral	None	None	None	None	N
T/G	0.3893	ambiguous	0.3713	ambiguous	-0.877	Destabilizing	0.404	N	0.473	neutral	None	None	None	None	N
T/H	0.7084	likely_pathogenic	0.673	pathogenic	-1.337	Destabilizing	0.947	D	0.546	neutral	None	None	None	None	N
T/I	0.893	likely_pathogenic	0.9027	pathogenic	0.295	Stabilizing	0.642	D	0.509	neutral	N	0.500583218	None	None	N
T/K	0.7056	likely_pathogenic	0.6695	pathogenic	-0.953	Destabilizing	0.404	N	0.506	neutral	None	None	None	None	N
T/L	0.4645	ambiguous	0.4623	ambiguous	0.295	Stabilizing	0.189	N	0.447	neutral	None	None	None	None	N
T/M	0.3497	ambiguous	0.3472	ambiguous	0.537	Stabilizing	0.088	N	0.469	neutral	None	None	None	None	N
T/N	0.4121	ambiguous	0.3948	ambiguous	-1.359	Destabilizing	0.007	N	0.327	neutral	N	0.502648132	None	None	N
T/P	0.9309	likely_pathogenic	0.9177	pathogenic	0.049	Stabilizing	0.879	D	0.523	neutral	N	0.515724958	None	None	N
T/Q	0.5808	likely_pathogenic	0.57	pathogenic	-1.319	Destabilizing	0.826	D	0.525	neutral	None	None	None	None	N
T/R	0.6221	likely_pathogenic	0.5942	pathogenic	-0.937	Destabilizing	0.826	D	0.533	neutral	None	None	None	None	N
T/S	0.2009	likely_benign	0.2038	benign	-1.326	Destabilizing	0.013	N	0.305	neutral	N	0.46891956	None	None	N
T/V	0.7036	likely_pathogenic	0.7281	pathogenic	0.049	Stabilizing	0.404	N	0.457	neutral	None	None	None	None	N
T/W	0.9596	likely_pathogenic	0.9481	pathogenic	-0.589	Destabilizing	0.991	D	0.57	neutral	None	None	None	None	N
T/Y	0.8415	likely_pathogenic	0.8222	pathogenic	-0.244	Destabilizing	0.906	D	0.57	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.