TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2593	8002;8003;8004	chr2:178773187;178773186;178773185	chr2:179637914;179637913;179637912
N2AB	2593	8002;8003;8004	chr2:178773187;178773186;178773185	chr2:179637914;179637913;179637912
N2A	2593	8002;8003;8004	chr2:178773187;178773186;178773185	chr2:179637914;179637913;179637912
N2B	2547	7864;7865;7866	chr2:178773187;178773186;178773185	chr2:179637914;179637913;179637912
Novex-1	2547	7864;7865;7866	chr2:178773187;178773186;178773185	chr2:179637914;179637913;179637912
Novex-2	2547	7864;7865;7866	chr2:178773187;178773186;178773185	chr2:179637914;179637913;179637912
Novex-3	2593	8002;8003;8004	chr2:178773187;178773186;178773185	chr2:179637914;179637913;179637912

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-15
• Domain position: 61
• Structural Position: 143
• Q(SASA): 0.7185
• 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
N/S	None	None	0.625	N	0.472	0.196	0.165133752707	gnomAD-4.0.0	1.59114E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02261E-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
N/A	0.4501	ambiguous	0.4737	ambiguous	-0.478	Destabilizing	0.842	D	0.443	neutral	None	None	None	None	N
N/C	0.5152	ambiguous	0.5618	ambiguous	0.423	Stabilizing	0.998	D	0.53	neutral	None	None	None	None	N
N/D	0.1714	likely_benign	0.1559	benign	-0.441	Destabilizing	0.005	N	0.111	neutral	N	0.446593972	None	None	N
N/E	0.5156	ambiguous	0.4969	ambiguous	-0.425	Destabilizing	0.525	D	0.415	neutral	None	None	None	None	N
N/F	0.7804	likely_pathogenic	0.7989	pathogenic	-0.553	Destabilizing	0.991	D	0.501	neutral	None	None	None	None	N
N/G	0.396	ambiguous	0.4141	ambiguous	-0.741	Destabilizing	0.688	D	0.427	neutral	None	None	None	None	N
N/H	0.1463	likely_benign	0.1574	benign	-0.765	Destabilizing	0.989	D	0.403	neutral	N	0.517848941	None	None	N
N/I	0.7052	likely_pathogenic	0.7123	pathogenic	0.154	Stabilizing	0.966	D	0.513	neutral	D	0.586288208	None	None	N
N/K	0.4213	ambiguous	0.4302	ambiguous	-0.152	Destabilizing	0.012	N	0.194	neutral	N	0.4557657	None	None	N
N/L	0.4775	ambiguous	0.5072	ambiguous	0.154	Stabilizing	0.949	D	0.473	neutral	None	None	None	None	N
N/M	0.6035	likely_pathogenic	0.6359	pathogenic	0.737	Stabilizing	0.998	D	0.476	neutral	None	None	None	None	N
N/P	0.8635	likely_pathogenic	0.8583	pathogenic	-0.028	Destabilizing	0.974	D	0.461	neutral	None	None	None	None	N
N/Q	0.4404	ambiguous	0.4583	ambiguous	-0.653	Destabilizing	0.949	D	0.374	neutral	None	None	None	None	N
N/R	0.4612	ambiguous	0.4689	ambiguous	-0.102	Destabilizing	0.728	D	0.403	neutral	None	None	None	None	N
N/S	0.1419	likely_benign	0.1496	benign	-0.439	Destabilizing	0.625	D	0.472	neutral	N	0.449293931	None	None	N
N/T	0.3371	likely_benign	0.3532	ambiguous	-0.268	Destabilizing	0.801	D	0.387	neutral	N	0.501143335	None	None	N
N/V	0.6679	likely_pathogenic	0.6891	pathogenic	-0.028	Destabilizing	0.974	D	0.477	neutral	None	None	None	None	N
N/W	0.8741	likely_pathogenic	0.8937	pathogenic	-0.452	Destabilizing	0.998	D	0.64	neutral	None	None	None	None	N
N/Y	0.2546	likely_benign	0.2643	benign	-0.227	Destabilizing	0.989	D	0.487	neutral	D	0.585552647	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.