TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31100	93523;93524;93525	chr2:178548328;178548327;178548326	chr2:179413055;179413054;179413053
N2AB	29459	88600;88601;88602	chr2:178548328;178548327;178548326	chr2:179413055;179413054;179413053
N2A	28532	85819;85820;85821	chr2:178548328;178548327;178548326	chr2:179413055;179413054;179413053
N2B	22035	66328;66329;66330	chr2:178548328;178548327;178548326	chr2:179413055;179413054;179413053
Novex-1	22160	66703;66704;66705	chr2:178548328;178548327;178548326	chr2:179413055;179413054;179413053
Novex-2	22227	66904;66905;66906	chr2:178548328;178548327;178548326	chr2:179413055;179413054;179413053
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: Fn3-114
• Domain position: 85
• Structural Position: 119
• Q(SASA): 0.538
• 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
E/K	None	None	0.999	N	0.677	0.384	0.351830644314	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	6.17284E-04	0	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	0.1976	likely_benign	0.195	benign	-0.615	Destabilizing	0.999	D	0.713	prob.delet.	N	0.468241686	None	None	I
E/C	0.8162	likely_pathogenic	0.826	pathogenic	-0.049	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
E/D	0.1336	likely_benign	0.1386	benign	-0.593	Destabilizing	0.999	D	0.571	neutral	N	0.487062604	None	None	I
E/F	0.744	likely_pathogenic	0.7077	pathogenic	-0.573	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	I
E/G	0.3099	likely_benign	0.2862	benign	-0.834	Destabilizing	1.0	D	0.729	prob.delet.	N	0.513324513	None	None	I
E/H	0.5979	likely_pathogenic	0.5413	ambiguous	-0.56	Destabilizing	1.0	D	0.648	neutral	None	None	None	None	I
E/I	0.2418	likely_benign	0.2253	benign	-0.064	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	I
E/K	0.2509	likely_benign	0.1923	benign	0.115	Stabilizing	0.999	D	0.677	prob.neutral	N	0.518057514	None	None	I
E/L	0.321	likely_benign	0.2918	benign	-0.064	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	I
E/M	0.3857	ambiguous	0.3639	ambiguous	0.238	Stabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	I
E/N	0.3112	likely_benign	0.2972	benign	-0.17	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
E/P	0.6453	likely_pathogenic	0.637	pathogenic	-0.228	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	I
E/Q	0.1691	likely_benign	0.1547	benign	-0.155	Destabilizing	1.0	D	0.695	prob.neutral	N	0.477876471	None	None	I
E/R	0.4194	ambiguous	0.3486	ambiguous	0.256	Stabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
E/S	0.2517	likely_benign	0.2427	benign	-0.349	Destabilizing	0.999	D	0.727	prob.delet.	None	None	None	None	I
E/T	0.2665	likely_benign	0.2557	benign	-0.175	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	I
E/V	0.1475	likely_benign	0.1389	benign	-0.228	Destabilizing	1.0	D	0.765	deleterious	N	0.494951368	None	None	I
E/W	0.9386	likely_pathogenic	0.9268	pathogenic	-0.416	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
E/Y	0.652	likely_pathogenic	0.6224	pathogenic	-0.331	Destabilizing	1.0	D	0.753	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.