TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16949	51070;51071;51072	chr2:178611384;178611383;178611382	chr2:179476111;179476110;179476109
N2AB	15308	46147;46148;46149	chr2:178611384;178611383;178611382	chr2:179476111;179476110;179476109
N2A	14381	43366;43367;43368	chr2:178611384;178611383;178611382	chr2:179476111;179476110;179476109
N2B	7884	23875;23876;23877	chr2:178611384;178611383;178611382	chr2:179476111;179476110;179476109
Novex-1	8009	24250;24251;24252	chr2:178611384;178611383;178611382	chr2:179476111;179476110;179476109
Novex-2	8076	24451;24452;24453	chr2:178611384;178611383;178611382	chr2:179476111;179476110;179476109
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: Fn3-11
• Domain position: 98
• Structural Position: 131
• Q(SASA): 0.4422
• 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
K/E	rs1368701506	0.222	0.992	N	0.581	0.284	0.292423486923	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
K/E	rs1368701506	0.222	0.992	N	0.581	0.284	0.292423486923	gnomAD-4.0.0	1.59344E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43332E-05	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
K/A	0.6045	likely_pathogenic	0.6641	pathogenic	-0.257	Destabilizing	0.964	D	0.498	neutral	None	None	None	None	N
K/C	0.8125	likely_pathogenic	0.8611	pathogenic	-0.206	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
K/D	0.882	likely_pathogenic	0.9045	pathogenic	-0.004	Destabilizing	0.998	D	0.591	neutral	None	None	None	None	N
K/E	0.4043	ambiguous	0.4683	ambiguous	0.045	Stabilizing	0.992	D	0.581	neutral	N	0.463963231	None	None	N
K/F	0.9353	likely_pathogenic	0.9542	pathogenic	-0.18	Destabilizing	0.995	D	0.771	deleterious	None	None	None	None	N
K/G	0.7382	likely_pathogenic	0.7836	pathogenic	-0.558	Destabilizing	0.998	D	0.512	neutral	None	None	None	None	N
K/H	0.5532	ambiguous	0.603	pathogenic	-0.985	Destabilizing	1.0	D	0.555	neutral	None	None	None	None	N
K/I	0.6328	likely_pathogenic	0.7084	pathogenic	0.488	Stabilizing	0.386	N	0.423	neutral	N	0.471659256	None	None	N
K/L	0.6935	likely_pathogenic	0.7363	pathogenic	0.488	Stabilizing	0.931	D	0.483	neutral	None	None	None	None	N
K/M	0.4747	ambiguous	0.5367	ambiguous	0.436	Stabilizing	0.999	D	0.531	neutral	None	None	None	None	N
K/N	0.7543	likely_pathogenic	0.8005	pathogenic	0.015	Stabilizing	0.998	D	0.585	neutral	D	0.589585652	None	None	N
K/P	0.9796	likely_pathogenic	0.9825	pathogenic	0.27	Stabilizing	0.998	D	0.563	neutral	None	None	None	None	N
K/Q	0.2382	likely_benign	0.2665	benign	-0.167	Destabilizing	0.998	D	0.611	neutral	N	0.469619813	None	None	N
K/R	0.0975	likely_benign	0.1026	benign	-0.34	Destabilizing	0.992	D	0.602	neutral	N	0.475243215	None	None	N
K/S	0.6826	likely_pathogenic	0.7388	pathogenic	-0.568	Destabilizing	0.994	D	0.627	neutral	None	None	None	None	N
K/T	0.3543	ambiguous	0.4193	ambiguous	-0.341	Destabilizing	0.993	D	0.579	neutral	N	0.507227346	None	None	N
K/V	0.5156	ambiguous	0.5914	pathogenic	0.27	Stabilizing	0.931	D	0.493	neutral	None	None	None	None	N
K/W	0.9226	likely_pathogenic	0.9409	pathogenic	-0.086	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
K/Y	0.8796	likely_pathogenic	0.9083	pathogenic	0.221	Stabilizing	0.998	D	0.704	prob.delet.	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.