TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14690	44293;44294;44295	chr2:178630890;178630889;178630888	chr2:179495617;179495616;179495615
N2AB	13049	39370;39371;39372	chr2:178630890;178630889;178630888	chr2:179495617;179495616;179495615
N2A	12122	36589;36590;36591	chr2:178630890;178630889;178630888	chr2:179495617;179495616;179495615
N2B	5625	17098;17099;17100	chr2:178630890;178630889;178630888	chr2:179495617;179495616;179495615
Novex-1	5750	17473;17474;17475	chr2:178630890;178630889;178630888	chr2:179495617;179495616;179495615
Novex-2	5817	17674;17675;17676	chr2:178630890;178630889;178630888	chr2:179495617;179495616;179495615
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-98
• Domain position: 16
• Structural Position: 25
• Q(SASA): 0.3401
• 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
E/G	None	None	0.986	N	0.682	0.352	0.288352970974	gnomAD-4.0.0	1.59243E-06	None	None	None	None	N	None	0	0	None	0	2.78164E-05	None	0	0	0	0	0
E/K	None	None	0.952	N	0.585	0.331	0.21737058555	gnomAD-4.0.0	1.59245E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86025E-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
E/A	0.4752	ambiguous	0.3806	ambiguous	-0.529	Destabilizing	0.952	D	0.657	prob.neutral	D	0.536176983	None	None	N
E/C	0.9834	likely_pathogenic	0.9719	pathogenic	0.029	Stabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
E/D	0.2789	likely_benign	0.2458	benign	-0.68	Destabilizing	0.058	N	0.247	neutral	N	0.433776786	None	None	N
E/F	0.987	likely_pathogenic	0.9748	pathogenic	-0.549	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
E/G	0.4559	ambiguous	0.3032	benign	-0.769	Destabilizing	0.986	D	0.682	prob.neutral	N	0.434108826	None	None	N
E/H	0.9148	likely_pathogenic	0.8574	pathogenic	-0.658	Destabilizing	1.0	D	0.637	neutral	None	None	None	None	N
E/I	0.9521	likely_pathogenic	0.9188	pathogenic	0.084	Stabilizing	0.995	D	0.8	deleterious	None	None	None	None	N
E/K	0.5318	ambiguous	0.3593	ambiguous	0.042	Stabilizing	0.952	D	0.585	neutral	N	0.471901188	None	None	N
E/L	0.9312	likely_pathogenic	0.8849	pathogenic	0.084	Stabilizing	0.995	D	0.752	deleterious	None	None	None	None	N
E/M	0.8884	likely_pathogenic	0.8381	pathogenic	0.454	Stabilizing	1.0	D	0.739	deleterious	None	None	None	None	N
E/N	0.6424	likely_pathogenic	0.5514	ambiguous	-0.212	Destabilizing	0.979	D	0.69	prob.delet.	None	None	None	None	N
E/P	0.9958	likely_pathogenic	0.9847	pathogenic	-0.099	Destabilizing	0.995	D	0.717	prob.delet.	None	None	None	None	N
E/Q	0.3481	ambiguous	0.2882	benign	-0.183	Destabilizing	0.993	D	0.672	prob.neutral	N	0.494073256	None	None	N
E/R	0.7391	likely_pathogenic	0.5767	pathogenic	0.149	Stabilizing	0.995	D	0.642	neutral	None	None	None	None	N
E/S	0.5342	ambiguous	0.4505	ambiguous	-0.408	Destabilizing	0.963	D	0.6	neutral	None	None	None	None	N
E/T	0.7481	likely_pathogenic	0.6393	pathogenic	-0.22	Destabilizing	0.995	D	0.709	prob.delet.	None	None	None	None	N
E/V	0.8149	likely_pathogenic	0.7361	pathogenic	-0.099	Destabilizing	0.993	D	0.729	deleterious	D	0.579856499	None	None	N
E/W	0.9965	likely_pathogenic	0.9915	pathogenic	-0.444	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
E/Y	0.9713	likely_pathogenic	0.9445	pathogenic	-0.32	Destabilizing	1.0	D	0.747	deleterious	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.