TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21956	66091;66092;66093	chr2:178582590;178582589;178582588	chr2:179447317;179447316;179447315
N2AB	20315	61168;61169;61170	chr2:178582590;178582589;178582588	chr2:179447317;179447316;179447315
N2A	19388	58387;58388;58389	chr2:178582590;178582589;178582588	chr2:179447317;179447316;179447315
N2B	12891	38896;38897;38898	chr2:178582590;178582589;178582588	chr2:179447317;179447316;179447315
Novex-1	13016	39271;39272;39273	chr2:178582590;178582589;178582588	chr2:179447317;179447316;179447315
Novex-2	13083	39472;39473;39474	chr2:178582590;178582589;178582588	chr2:179447317;179447316;179447315
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-47
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.5649
• 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
K/T	rs779688235	-0.184	0.993	N	0.595	0.097	0.197625483188	gnomAD-2.1.1	2.08E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	3.68E-05	1.72354E-04
K/T	rs779688235	-0.184	0.993	N	0.595	0.097	0.197625483188	gnomAD-3.1.2	1.97E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	4.41E-05	0	0
K/T	rs779688235	-0.184	0.993	N	0.595	0.097	0.197625483188	gnomAD-4.0.0	1.6212E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.12929E-05	0	1.61134E-05

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
K/A	0.8252	likely_pathogenic	0.7908	pathogenic	-0.183	Destabilizing	0.982	D	0.531	neutral	None	None	None	None	I
K/C	0.8426	likely_pathogenic	0.7968	pathogenic	-0.225	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	I
K/D	0.9821	likely_pathogenic	0.9813	pathogenic	0.046	Stabilizing	0.999	D	0.633	neutral	None	None	None	None	I
K/E	0.76	likely_pathogenic	0.7385	pathogenic	0.058	Stabilizing	0.996	D	0.557	neutral	N	0.471518644	None	None	I
K/F	0.97	likely_pathogenic	0.9621	pathogenic	-0.354	Destabilizing	0.997	D	0.802	deleterious	None	None	None	None	I
K/G	0.9493	likely_pathogenic	0.9414	pathogenic	-0.418	Destabilizing	0.999	D	0.489	neutral	None	None	None	None	I
K/H	0.7029	likely_pathogenic	0.6702	pathogenic	-0.793	Destabilizing	1.0	D	0.615	neutral	None	None	None	None	I
K/I	0.5323	ambiguous	0.4789	ambiguous	0.366	Stabilizing	0.986	D	0.561	neutral	N	0.477546538	None	None	I
K/L	0.7554	likely_pathogenic	0.71	pathogenic	0.366	Stabilizing	0.965	D	0.512	neutral	None	None	None	None	I
K/M	0.563	ambiguous	0.4968	ambiguous	0.394	Stabilizing	0.999	D	0.592	neutral	None	None	None	None	I
K/N	0.9249	likely_pathogenic	0.9173	pathogenic	0.175	Stabilizing	0.999	D	0.636	neutral	N	0.465442258	None	None	I
K/P	0.9622	likely_pathogenic	0.9576	pathogenic	0.212	Stabilizing	0.999	D	0.636	neutral	None	None	None	None	I
K/Q	0.3991	ambiguous	0.3676	ambiguous	-0.091	Destabilizing	0.999	D	0.664	prob.neutral	N	0.472025624	None	None	I
K/R	0.0984	likely_benign	0.0956	benign	-0.068	Destabilizing	0.996	D	0.613	neutral	N	0.451725374	None	None	I
K/S	0.8982	likely_pathogenic	0.8782	pathogenic	-0.418	Destabilizing	0.991	D	0.64	neutral	None	None	None	None	I
K/T	0.4515	ambiguous	0.3914	ambiguous	-0.246	Destabilizing	0.993	D	0.595	neutral	N	0.478623974	None	None	I
K/V	0.4617	ambiguous	0.4119	ambiguous	0.212	Stabilizing	0.628	D	0.373	neutral	None	None	None	None	I
K/W	0.9749	likely_pathogenic	0.9668	pathogenic	-0.265	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
K/Y	0.9393	likely_pathogenic	0.9185	pathogenic	0.08	Stabilizing	0.999	D	0.775	deleterious	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.