TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17107	51544;51545;51546	chr2:178610207;178610206;178610205	chr2:179474934;179474933;179474932
N2AB	15466	46621;46622;46623	chr2:178610207;178610206;178610205	chr2:179474934;179474933;179474932
N2A	14539	43840;43841;43842	chr2:178610207;178610206;178610205	chr2:179474934;179474933;179474932
N2B	8042	24349;24350;24351	chr2:178610207;178610206;178610205	chr2:179474934;179474933;179474932
Novex-1	8167	24724;24725;24726	chr2:178610207;178610206;178610205	chr2:179474934;179474933;179474932
Novex-2	8234	24925;24926;24927	chr2:178610207;178610206;178610205	chr2:179474934;179474933;179474932
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: Fn3-12
• Domain position: 61
• Structural Position: 92
• Q(SASA): 0.2577
• 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/P	None	None	0.001	N	0.247	0.327	0.270889551736	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
T/S	None	None	0.007	N	0.169	0.114	0.224531998449	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.0827	likely_benign	0.0914	benign	-0.933	Destabilizing	0.003	N	0.165	neutral	D	0.52283419	None	None	N
T/C	0.3275	likely_benign	0.3294	benign	-0.498	Destabilizing	0.983	D	0.476	neutral	None	None	None	None	N
T/D	0.4032	ambiguous	0.452	ambiguous	0.024	Stabilizing	0.264	N	0.426	neutral	None	None	None	None	N
T/E	0.3146	likely_benign	0.3465	ambiguous	0.057	Stabilizing	0.129	N	0.391	neutral	None	None	None	None	N
T/F	0.229	likely_benign	0.2423	benign	-0.933	Destabilizing	0.836	D	0.527	neutral	None	None	None	None	N
T/G	0.2519	likely_benign	0.2682	benign	-1.217	Destabilizing	0.129	N	0.385	neutral	None	None	None	None	N
T/H	0.2476	likely_benign	0.2526	benign	-1.37	Destabilizing	0.716	D	0.528	neutral	None	None	None	None	N
T/I	0.1034	likely_benign	0.1066	benign	-0.259	Destabilizing	0.794	D	0.519	neutral	N	0.521140679	None	None	N
T/K	0.3368	likely_benign	0.3702	ambiguous	-0.62	Destabilizing	0.264	N	0.407	neutral	None	None	None	None	N
T/L	0.0842	likely_benign	0.0861	benign	-0.259	Destabilizing	0.418	N	0.424	neutral	None	None	None	None	N
T/M	0.0726	likely_benign	0.0737	benign	-0.08	Destabilizing	0.836	D	0.492	neutral	None	None	None	None	N
T/N	0.0836	likely_benign	0.096	benign	-0.631	Destabilizing	0.001	N	0.167	neutral	N	0.521140679	None	None	N
T/P	0.1361	likely_benign	0.167	benign	-0.451	Destabilizing	0.001	N	0.247	neutral	N	0.503595068	None	None	N
T/Q	0.214	likely_benign	0.2109	benign	-0.697	Destabilizing	0.01	N	0.314	neutral	None	None	None	None	N
T/R	0.328	likely_benign	0.3738	ambiguous	-0.458	Destabilizing	0.264	N	0.477	neutral	None	None	None	None	N
T/S	0.1086	likely_benign	0.1217	benign	-0.972	Destabilizing	0.007	N	0.169	neutral	N	0.47243933	None	None	N
T/V	0.0863	likely_benign	0.0882	benign	-0.451	Destabilizing	0.418	N	0.349	neutral	None	None	None	None	N
T/W	0.5777	likely_pathogenic	0.5807	pathogenic	-0.873	Destabilizing	0.983	D	0.565	neutral	None	None	None	None	N
T/Y	0.2678	likely_benign	0.275	benign	-0.636	Destabilizing	0.94	D	0.529	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.