TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13939	42040;42041;42042	chr2:178635509;178635508;178635507	chr2:179500236;179500235;179500234
N2AB	12298	37117;37118;37119	chr2:178635509;178635508;178635507	chr2:179500236;179500235;179500234
N2A	11371	34336;34337;34338	chr2:178635509;178635508;178635507	chr2:179500236;179500235;179500234
N2B	4874	14845;14846;14847	chr2:178635509;178635508;178635507	chr2:179500236;179500235;179500234
Novex-1	4999	15220;15221;15222	chr2:178635509;178635508;178635507	chr2:179500236;179500235;179500234
Novex-2	5066	15421;15422;15423	chr2:178635509;178635508;178635507	chr2:179500236;179500235;179500234
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-89
• Domain position: 64
• Structural Position: 146
• Q(SASA): 0.5339
• 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
P/S	None	None	1.0	N	0.819	0.343	0.209622950755	gnomAD-4.0.0	1.6204E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.46297E-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
P/A	0.199	likely_benign	0.1886	benign	-0.277	Destabilizing	0.999	D	0.787	deleterious	N	0.516145356	None	None	N
P/C	0.9511	likely_pathogenic	0.9536	pathogenic	-0.396	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
P/D	0.7873	likely_pathogenic	0.7497	pathogenic	-0.479	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
P/E	0.5296	ambiguous	0.4984	ambiguous	-0.602	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
P/F	0.9014	likely_pathogenic	0.8974	pathogenic	-0.653	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
P/G	0.7196	likely_pathogenic	0.7134	pathogenic	-0.382	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
P/H	0.6851	likely_pathogenic	0.6429	pathogenic	-0.076	Destabilizing	1.0	D	0.739	deleterious	None	None	None	None	N
P/I	0.6199	likely_pathogenic	0.6591	pathogenic	-0.152	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
P/K	0.7355	likely_pathogenic	0.7084	pathogenic	-0.341	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
P/L	0.2706	likely_benign	0.2727	benign	-0.152	Destabilizing	1.0	D	0.752	deleterious	N	0.434098847	None	None	N
P/M	0.6234	likely_pathogenic	0.6491	pathogenic	-0.275	Destabilizing	1.0	D	0.733	deleterious	None	None	None	None	N
P/N	0.7559	likely_pathogenic	0.7537	pathogenic	0.021	Stabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
P/Q	0.4805	ambiguous	0.4336	ambiguous	-0.241	Destabilizing	1.0	D	0.833	deleterious	D	0.523210961	None	None	N
P/R	0.644	likely_pathogenic	0.578	pathogenic	0.153	Stabilizing	1.0	D	0.765	deleterious	N	0.514943615	None	None	N
P/S	0.4562	ambiguous	0.4349	ambiguous	-0.242	Destabilizing	1.0	D	0.819	deleterious	N	0.520529379	None	None	N
P/T	0.3519	ambiguous	0.348	ambiguous	-0.275	Destabilizing	1.0	D	0.796	deleterious	N	0.435146116	None	None	N
P/V	0.4562	ambiguous	0.4847	ambiguous	-0.161	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
P/W	0.9534	likely_pathogenic	0.9449	pathogenic	-0.759	Destabilizing	1.0	D	0.69	prob.delet.	None	None	None	None	N
P/Y	0.8799	likely_pathogenic	0.8653	pathogenic	-0.443	Destabilizing	1.0	D	0.784	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.