TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7871	23836;23837;23838	chr2:178720031;178720030;178720029	chr2:179584758;179584757;179584756
N2AB	7554	22885;22886;22887	chr2:178720031;178720030;178720029	chr2:179584758;179584757;179584756
N2A	6627	20104;20105;20106	chr2:178720031;178720030;178720029	chr2:179584758;179584757;179584756
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: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-63
• Domain position: 77
• Structural Position: 159
• Q(SASA): 0.6148
• 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
K/I	None	None	0.002	D	0.519	0.341	0.482137172311	gnomAD-4.0.0	1.36896E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99747E-07	1.15982E-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	0.7768	likely_pathogenic	0.5725	pathogenic	-0.548	Destabilizing	0.042	N	0.362	neutral	None	None	None	None	I
K/C	0.9102	likely_pathogenic	0.7971	pathogenic	-0.685	Destabilizing	0.945	D	0.452	neutral	None	None	None	None	I
K/D	0.9492	likely_pathogenic	0.8626	pathogenic	-0.412	Destabilizing	0.095	N	0.407	neutral	None	None	None	None	I
K/E	0.4972	ambiguous	0.2954	benign	-0.324	Destabilizing	0.001	N	0.123	neutral	N	0.480590496	None	None	I
K/F	0.9549	likely_pathogenic	0.8821	pathogenic	-0.433	Destabilizing	0.227	N	0.484	neutral	None	None	None	None	I
K/G	0.8431	likely_pathogenic	0.6514	pathogenic	-0.892	Destabilizing	0.042	N	0.435	neutral	None	None	None	None	I
K/H	0.5902	likely_pathogenic	0.404	ambiguous	-1.347	Destabilizing	0.234	N	0.451	neutral	None	None	None	None	I
K/I	0.7491	likely_pathogenic	0.5664	pathogenic	0.328	Stabilizing	0.002	N	0.519	neutral	D	0.533118259	None	None	I
K/L	0.7788	likely_pathogenic	0.6109	pathogenic	0.328	Stabilizing	0.001	N	0.432	neutral	None	None	None	None	I
K/M	0.573	likely_pathogenic	0.3842	ambiguous	0.323	Stabilizing	0.002	N	0.306	neutral	None	None	None	None	I
K/N	0.8476	likely_pathogenic	0.6686	pathogenic	-0.518	Destabilizing	None	N	0.175	neutral	N	0.501647899	None	None	I
K/P	0.9928	likely_pathogenic	0.98	pathogenic	0.066	Stabilizing	0.299	N	0.482	neutral	None	None	None	None	I
K/Q	0.222	likely_benign	0.1423	benign	-0.685	Destabilizing	None	N	0.185	neutral	N	0.498408253	None	None	I
K/R	0.0977	likely_benign	0.0809	benign	-0.614	Destabilizing	None	N	0.189	neutral	N	0.517975448	None	None	I
K/S	0.7527	likely_pathogenic	0.5313	ambiguous	-1.146	Destabilizing	0.042	N	0.346	neutral	None	None	None	None	I
K/T	0.4383	ambiguous	0.2481	benign	-0.862	Destabilizing	0.001	N	0.213	neutral	N	0.495538519	None	None	I
K/V	0.7065	likely_pathogenic	0.5289	ambiguous	0.066	Stabilizing	None	N	0.245	neutral	None	None	None	None	I
K/W	0.9208	likely_pathogenic	0.8181	pathogenic	-0.317	Destabilizing	0.962	D	0.473	neutral	None	None	None	None	I
K/Y	0.8968	likely_pathogenic	0.7817	pathogenic	0.024	Stabilizing	0.065	N	0.472	neutral	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.