TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16503	49732;49733;49734	chr2:178613776;178613775;178613774	chr2:179478503;179478502;179478501
N2AB	14862	44809;44810;44811	chr2:178613776;178613775;178613774	chr2:179478503;179478502;179478501
N2A	13935	42028;42029;42030	chr2:178613776;178613775;178613774	chr2:179478503;179478502;179478501
N2B	7438	22537;22538;22539	chr2:178613776;178613775;178613774	chr2:179478503;179478502;179478501
Novex-1	7563	22912;22913;22914	chr2:178613776;178613775;178613774	chr2:179478503;179478502;179478501
Novex-2	7630	23113;23114;23115	chr2:178613776;178613775;178613774	chr2:179478503;179478502;179478501
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Fn3-7
• Domain position: 54
• Structural Position: 72
• Q(SASA): 0.5546
• 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
M/T	None	None	0.425	N	0.317	0.267	0.662192778189	gnomAD-4.0.0	1.59411E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86431E-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
M/A	0.7114	likely_pathogenic	0.3909	ambiguous	-0.425	Destabilizing	0.495	N	0.251	neutral	None	None	None	None	I
M/C	0.9089	likely_pathogenic	0.7105	pathogenic	-0.463	Destabilizing	0.981	D	0.283	neutral	None	None	None	None	I
M/D	0.9516	likely_pathogenic	0.8433	pathogenic	0.175	Stabilizing	0.981	D	0.407	neutral	None	None	None	None	I
M/E	0.8284	likely_pathogenic	0.6638	pathogenic	0.14	Stabilizing	0.936	D	0.392	neutral	None	None	None	None	I
M/F	0.4962	ambiguous	0.306	benign	-0.102	Destabilizing	0.704	D	0.2	neutral	None	None	None	None	I
M/G	0.8931	likely_pathogenic	0.6321	pathogenic	-0.584	Destabilizing	0.936	D	0.411	neutral	None	None	None	None	I
M/H	0.785	likely_pathogenic	0.5269	ambiguous	0.266	Stabilizing	0.981	D	0.275	neutral	None	None	None	None	I
M/I	0.377	ambiguous	0.2186	benign	-0.089	Destabilizing	0.001	N	0.076	neutral	N	0.362367545	None	None	I
M/K	0.5084	ambiguous	0.43	ambiguous	0.277	Stabilizing	0.784	D	0.349	neutral	N	0.346288546	None	None	I
M/L	0.1471	likely_benign	0.1036	benign	-0.089	Destabilizing	0.001	N	0.069	neutral	N	0.325464705	None	None	I
M/N	0.6924	likely_pathogenic	0.3594	ambiguous	0.341	Stabilizing	0.981	D	0.375	neutral	None	None	None	None	I
M/P	0.9791	likely_pathogenic	0.9326	pathogenic	-0.175	Destabilizing	0.981	D	0.379	neutral	None	None	None	None	I
M/Q	0.4931	ambiguous	0.3197	benign	0.216	Stabilizing	0.981	D	0.246	neutral	None	None	None	None	I
M/R	0.5857	likely_pathogenic	0.503	ambiguous	0.755	Stabilizing	0.917	D	0.407	neutral	N	0.382787247	None	None	I
M/S	0.7028	likely_pathogenic	0.3532	ambiguous	-0.07	Destabilizing	0.828	D	0.331	neutral	None	None	None	None	I
M/T	0.5436	ambiguous	0.237	benign	-0.008	Destabilizing	0.425	N	0.317	neutral	N	0.312892126	None	None	I
M/V	0.1747	likely_benign	0.1135	benign	-0.175	Destabilizing	0.065	N	0.191	neutral	N	0.329769903	None	None	I
M/W	0.878	likely_pathogenic	0.7268	pathogenic	-0.116	Destabilizing	0.995	D	0.281	neutral	None	None	None	None	I
M/Y	0.7383	likely_pathogenic	0.516	ambiguous	0.037	Stabilizing	0.981	D	0.382	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.