TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3901	11926;11927;11928	chr2:178741532;178741531;178741530	chr2:179606259;179606258;179606257
N2AB	3584	10975;10976;10977	chr2:178741532;178741531;178741530	chr2:179606259;179606258;179606257
N2A	None	None	chr2:None	chr2:None
N2B	3538	10837;10838;10839	chr2:178741532;178741531;178741530	chr2:179606259;179606258;179606257
Novex-1	3663	11212;11213;11214	chr2:178741532;178741531;178741530	chr2:179606259;179606258;179606257
Novex-2	3730	11413;11414;11415	chr2:178741532;178741531;178741530	chr2:179606259;179606258;179606257
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-27
• Domain position: 82
• Structural Position: 166
• Q(SASA): 0.2046
• Predicted PPI site: I

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	rs1388046179	0.102	None	N	0.328	0.216	None	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
T/I	rs1388046179	0.102	None	N	0.328	0.216	None	gnomAD-4.0.0	1.36839E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79889E-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	0.0673	likely_benign	0.0626	benign	-0.824	Destabilizing	None	N	0.109	neutral	N	0.386442687	None	None	I
T/C	0.4007	ambiguous	0.4181	ambiguous	-0.478	Destabilizing	0.356	N	0.569	neutral	None	None	None	None	I
T/D	0.3419	ambiguous	0.3046	benign	-0.199	Destabilizing	0.072	N	0.634	neutral	None	None	None	None	I
T/E	0.2713	likely_benign	0.2489	benign	-0.117	Destabilizing	0.038	N	0.578	neutral	None	None	None	None	I
T/F	0.3107	likely_benign	0.2858	benign	-0.643	Destabilizing	0.214	N	0.707	prob.neutral	None	None	None	None	I
T/G	0.2722	likely_benign	0.25	benign	-1.157	Destabilizing	0.016	N	0.636	neutral	None	None	None	None	I
T/H	0.2985	likely_benign	0.2807	benign	-1.254	Destabilizing	0.676	D	0.653	neutral	None	None	None	None	I
T/I	0.1901	likely_benign	0.1732	benign	-0.001	Destabilizing	None	N	0.328	neutral	N	0.473029838	None	None	I
T/K	0.2087	likely_benign	0.202	benign	-0.551	Destabilizing	0.029	N	0.577	neutral	N	0.499866909	None	None	I
T/L	0.1593	likely_benign	0.1489	benign	-0.001	Destabilizing	0.006	N	0.474	neutral	None	None	None	None	I
T/M	0.0965	likely_benign	0.094	benign	0.004	Stabilizing	0.007	N	0.385	neutral	None	None	None	None	I
T/N	0.1283	likely_benign	0.1182	benign	-0.733	Destabilizing	0.038	N	0.559	neutral	None	None	None	None	I
T/P	0.6664	likely_pathogenic	0.5906	pathogenic	-0.242	Destabilizing	0.171	N	0.625	neutral	N	0.511338012	None	None	I
T/Q	0.2246	likely_benign	0.2265	benign	-0.703	Destabilizing	0.214	N	0.626	neutral	None	None	None	None	I
T/R	0.1485	likely_benign	0.1415	benign	-0.475	Destabilizing	0.171	N	0.623	neutral	N	0.490463026	None	None	I
T/S	0.1222	likely_benign	0.1127	benign	-1.044	Destabilizing	None	N	0.135	neutral	N	0.434813878	None	None	I
T/V	0.1503	likely_benign	0.1397	benign	-0.242	Destabilizing	0.006	N	0.399	neutral	None	None	None	None	I
T/W	0.6823	likely_pathogenic	0.6767	pathogenic	-0.661	Destabilizing	0.864	D	0.668	neutral	None	None	None	None	I
T/Y	0.2979	likely_benign	0.2881	benign	-0.373	Destabilizing	0.356	N	0.691	prob.neutral	None	None	None	None	I

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.