TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5924	17995;17996;17997	chr2:178730763;178730762;178730761	chr2:179595490;179595489;179595488
N2AB	5607	17044;17045;17046	chr2:178730763;178730762;178730761	chr2:179595490;179595489;179595488
N2A	4680	14263;14264;14265	chr2:178730763;178730762;178730761	chr2:179595490;179595489;179595488
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: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-43
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.4506
• 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	None	None	0.41	N	0.552	0.29	0.437314048365	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
K/N	rs1336731959	None	0.83	N	0.661	0.347	0.303453137403	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/N	rs1336731959	None	0.83	N	0.661	0.347	0.303453137403	gnomAD-4.0.0	6.88028E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.04007E-07	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
K/A	0.6178	likely_pathogenic	0.5718	pathogenic	-0.532	Destabilizing	0.648	D	0.601	neutral	None	None	None	None	N
K/C	0.8926	likely_pathogenic	0.8383	pathogenic	-0.494	Destabilizing	0.993	D	0.715	prob.delet.	None	None	None	None	N
K/D	0.8084	likely_pathogenic	0.8177	pathogenic	0.253	Stabilizing	0.866	D	0.736	prob.delet.	None	None	None	None	N
K/E	0.4278	ambiguous	0.4015	ambiguous	0.366	Stabilizing	0.41	N	0.552	neutral	N	0.520418321	None	None	N
K/F	0.9105	likely_pathogenic	0.8798	pathogenic	-0.204	Destabilizing	0.98	D	0.713	prob.delet.	None	None	None	None	N
K/G	0.6603	likely_pathogenic	0.6408	pathogenic	-0.878	Destabilizing	0.866	D	0.595	neutral	None	None	None	None	N
K/H	0.4692	ambiguous	0.4151	ambiguous	-1.031	Destabilizing	0.98	D	0.703	prob.neutral	None	None	None	None	N
K/I	0.6637	likely_pathogenic	0.5663	pathogenic	0.357	Stabilizing	0.929	D	0.743	deleterious	None	None	None	None	N
K/L	0.6394	likely_pathogenic	0.5511	ambiguous	0.357	Stabilizing	0.866	D	0.595	neutral	None	None	None	None	N
K/M	0.4231	ambiguous	0.3628	ambiguous	0.086	Stabilizing	0.991	D	0.706	prob.neutral	N	0.508093133	None	None	N
K/N	0.6061	likely_pathogenic	0.6094	pathogenic	-0.228	Destabilizing	0.83	D	0.661	neutral	N	0.497293032	None	None	N
K/P	0.5475	ambiguous	0.5716	pathogenic	0.09	Stabilizing	0.929	D	0.743	deleterious	None	None	None	None	N
K/Q	0.2159	likely_benign	0.1826	benign	-0.252	Destabilizing	0.709	D	0.646	neutral	N	0.485327616	None	None	N
K/R	0.1054	likely_benign	0.0943	benign	-0.354	Destabilizing	0.01	N	0.246	neutral	N	0.504507506	None	None	N
K/S	0.6815	likely_pathogenic	0.6589	pathogenic	-0.914	Destabilizing	0.648	D	0.607	neutral	None	None	None	None	N
K/T	0.3687	ambiguous	0.3295	benign	-0.593	Destabilizing	0.83	D	0.686	prob.neutral	D	0.523093267	None	None	N
K/V	0.6172	likely_pathogenic	0.5339	ambiguous	0.09	Stabilizing	0.866	D	0.719	prob.delet.	None	None	None	None	N
K/W	0.8922	likely_pathogenic	0.8343	pathogenic	-0.081	Destabilizing	0.993	D	0.718	prob.delet.	None	None	None	None	N
K/Y	0.7699	likely_pathogenic	0.7166	pathogenic	0.188	Stabilizing	0.929	D	0.713	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.