TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9768	29527;29528;29529	chr2:178706572;178706571;178706570	chr2:179571299;179571298;179571297
N2AB	9451	28576;28577;28578	chr2:178706572;178706571;178706570	chr2:179571299;179571298;179571297
N2A	8524	25795;25796;25797	chr2:178706572;178706571;178706570	chr2:179571299;179571298;179571297
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: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Ig-83
• Domain position: 71
• Structural Position: 153
• Q(SASA): 0.2778
• 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
L/F	None	None	0.927	None	0.478	0.289	0.151104730317	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
L/A	0.4432	ambiguous	0.3081	benign	-1.62	Destabilizing	0.329	N	0.381	neutral	None	None	None	None	N
L/C	0.8084	likely_pathogenic	0.6633	pathogenic	-1.009	Destabilizing	0.995	D	0.507	neutral	None	None	None	None	N
L/D	0.8535	likely_pathogenic	0.7147	pathogenic	-0.679	Destabilizing	0.704	D	0.511	neutral	None	None	None	None	N
L/E	0.5918	likely_pathogenic	0.4211	ambiguous	-0.678	Destabilizing	0.329	N	0.443	neutral	None	None	None	None	N
L/F	0.2806	likely_benign	0.1735	benign	-1.203	Destabilizing	0.927	D	0.478	neutral	None	None	None	None	N
L/G	0.8039	likely_pathogenic	0.6158	pathogenic	-1.936	Destabilizing	0.704	D	0.495	neutral	None	None	None	None	N
L/H	0.4183	ambiguous	0.2639	benign	-1.084	Destabilizing	0.944	D	0.55	neutral	None	None	None	None	N
L/I	0.1172	likely_benign	0.0987	benign	-0.834	Destabilizing	0.642	D	0.4	neutral	None	None	None	None	N
L/K	0.4695	ambiguous	0.3251	benign	-0.912	Destabilizing	0.329	N	0.46	neutral	None	None	None	None	N
L/M	0.147	likely_benign	0.1171	benign	-0.617	Destabilizing	0.944	D	0.49	neutral	None	None	None	None	N
L/N	0.4541	ambiguous	0.3328	benign	-0.727	Destabilizing	0.704	D	0.533	neutral	None	None	None	None	N
L/P	0.7065	likely_pathogenic	0.4661	ambiguous	-1.064	Destabilizing	0.003	N	0.391	neutral	None	None	None	None	N
L/Q	0.2293	likely_benign	0.1599	benign	-0.905	Destabilizing	0.004	N	0.296	neutral	None	None	None	None	N
L/R	0.4109	ambiguous	0.2524	benign	-0.349	Destabilizing	0.543	D	0.499	neutral	None	None	None	None	N
L/S	0.4181	ambiguous	0.2645	benign	-1.432	Destabilizing	0.27	N	0.453	neutral	None	None	None	None	N
L/T	0.2811	likely_benign	0.2136	benign	-1.309	Destabilizing	0.013	N	0.213	neutral	None	None	None	None	N
L/V	0.1371	likely_benign	0.1116	benign	-1.064	Destabilizing	0.27	N	0.425	neutral	None	None	None	None	N
L/W	0.4936	ambiguous	0.2934	benign	-1.226	Destabilizing	0.995	D	0.551	neutral	None	None	None	None	N
L/Y	0.5888	likely_pathogenic	0.3972	ambiguous	-0.995	Destabilizing	0.981	D	0.537	neutral	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.