TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6094	18505;18506;18507	chr2:178730120;178730119;178730118	chr2:179594847;179594846;179594845
N2AB	5777	17554;17555;17556	chr2:178730120;178730119;178730118	chr2:179594847;179594846;179594845
N2A	4850	14773;14774;14775	chr2:178730120;178730119;178730118	chr2:179594847;179594846;179594845
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-44
• Domain position: 83
• Structural Position: 168
• Q(SASA): 0.2636
• 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	rs1315540030	-0.069	0.317	N	0.519	0.311	0.386882687439	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
T/I	rs1315540030	-0.069	0.317	N	0.519	0.311	0.386882687439	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	rs1315540030	-0.069	0.317	N	0.519	0.311	0.386882687439	gnomAD-4.0.0	2.02997E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.40989E-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	0.0792	likely_benign	0.082	benign	-0.877	Destabilizing	None	N	0.221	neutral	N	0.477072975	None	None	N
T/C	0.485	ambiguous	0.4346	ambiguous	-0.501	Destabilizing	0.824	D	0.509	neutral	None	None	None	None	N
T/D	0.31	likely_benign	0.332	benign	0.287	Stabilizing	0.081	N	0.457	neutral	None	None	None	None	N
T/E	0.2668	likely_benign	0.2621	benign	0.308	Stabilizing	0.081	N	0.438	neutral	None	None	None	None	N
T/F	0.1891	likely_benign	0.1812	benign	-0.981	Destabilizing	0.555	D	0.561	neutral	None	None	None	None	N
T/G	0.2647	likely_benign	0.2804	benign	-1.135	Destabilizing	0.035	N	0.49	neutral	None	None	None	None	N
T/H	0.2536	likely_benign	0.2407	benign	-1.258	Destabilizing	0.824	D	0.552	neutral	None	None	None	None	N
T/I	0.1418	likely_benign	0.1318	benign	-0.281	Destabilizing	0.317	N	0.519	neutral	N	0.489156838	None	None	N
T/K	0.2224	likely_benign	0.2093	benign	-0.464	Destabilizing	0.081	N	0.44	neutral	None	None	None	None	N
T/L	0.1092	likely_benign	0.1103	benign	-0.281	Destabilizing	0.081	N	0.465	neutral	None	None	None	None	N
T/M	0.1064	likely_benign	0.1013	benign	-0.18	Destabilizing	0.791	D	0.518	neutral	None	None	None	None	N
T/N	0.109	likely_benign	0.1172	benign	-0.47	Destabilizing	0.062	N	0.449	neutral	N	0.472032515	None	None	N
T/P	0.2038	likely_benign	0.2637	benign	-0.448	Destabilizing	0.317	N	0.525	neutral	N	0.507742599	None	None	N
T/Q	0.2188	likely_benign	0.2152	benign	-0.542	Destabilizing	0.38	N	0.537	neutral	None	None	None	None	N
T/R	0.1866	likely_benign	0.1776	benign	-0.3	Destabilizing	0.38	N	0.529	neutral	None	None	None	None	N
T/S	0.0866	likely_benign	0.0908	benign	-0.832	Destabilizing	None	N	0.251	neutral	N	0.384373458	None	None	N
T/V	0.1162	likely_benign	0.1124	benign	-0.448	Destabilizing	0.081	N	0.474	neutral	None	None	None	None	N
T/W	0.5727	likely_pathogenic	0.5632	ambiguous	-0.914	Destabilizing	0.935	D	0.611	neutral	None	None	None	None	N
T/Y	0.2315	likely_benign	0.2218	benign	-0.66	Destabilizing	0.555	D	0.556	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.