TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8192	24799;24800;24801	chr2:178718532;178718531;178718530	chr2:179583259;179583258;179583257
N2AB	7875	23848;23849;23850	chr2:178718532;178718531;178718530	chr2:179583259;179583258;179583257
N2A	6948	21067;21068;21069	chr2:178718532;178718531;178718530	chr2:179583259;179583258;179583257
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: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-67
• Domain position: 22
• Structural Position: 33
• Q(SASA): 0.1511
• 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
A/S	rs2077844059	None	0.001	N	0.339	0.045	0.107399877778	gnomAD-4.0.0	1.5915E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85858E-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
A/C	0.4484	ambiguous	0.4577	ambiguous	-0.725	Destabilizing	None	N	0.335	neutral	None	None	None	None	N
A/D	0.9435	likely_pathogenic	0.9314	pathogenic	-2.25	Highly Destabilizing	0.175	N	0.727	prob.delet.	N	0.465201995	None	None	N
A/E	0.9374	likely_pathogenic	0.9262	pathogenic	-1.985	Destabilizing	0.22	N	0.679	prob.neutral	None	None	None	None	N
A/F	0.8352	likely_pathogenic	0.8201	pathogenic	-0.425	Destabilizing	0.497	N	0.773	deleterious	None	None	None	None	N
A/G	0.1587	likely_benign	0.1368	benign	-1.362	Destabilizing	0.042	N	0.614	neutral	N	0.468543053	None	None	N
A/H	0.971	likely_pathogenic	0.9648	pathogenic	-2.037	Highly Destabilizing	0.667	D	0.79	deleterious	None	None	None	None	N
A/I	0.4658	ambiguous	0.4691	ambiguous	0.655	Stabilizing	0.124	N	0.681	prob.neutral	None	None	None	None	N
A/K	0.9868	likely_pathogenic	0.9835	pathogenic	-0.81	Destabilizing	0.124	N	0.684	prob.neutral	None	None	None	None	N
A/L	0.4639	ambiguous	0.4489	ambiguous	0.655	Stabilizing	0.055	N	0.643	neutral	None	None	None	None	N
A/M	0.5269	ambiguous	0.492	ambiguous	0.304	Stabilizing	0.025	N	0.598	neutral	None	None	None	None	N
A/N	0.8002	likely_pathogenic	0.7658	pathogenic	-1.291	Destabilizing	0.124	N	0.735	prob.delet.	None	None	None	None	N
A/P	0.977	likely_pathogenic	0.9713	pathogenic	0.204	Stabilizing	0.602	D	0.753	deleterious	N	0.465201995	None	None	N
A/Q	0.9433	likely_pathogenic	0.9347	pathogenic	-0.955	Destabilizing	0.497	N	0.75	deleterious	None	None	None	None	N
A/R	0.9762	likely_pathogenic	0.9719	pathogenic	-1.174	Destabilizing	0.497	N	0.756	deleterious	None	None	None	None	N
A/S	0.153	likely_benign	0.1451	benign	-1.661	Destabilizing	0.001	N	0.339	neutral	N	0.454632393	None	None	N
A/T	0.1389	likely_benign	0.1192	benign	-1.256	Destabilizing	0.001	N	0.399	neutral	N	0.505637217	None	None	N
A/V	0.1996	likely_benign	0.1994	benign	0.204	Stabilizing	0.042	N	0.615	neutral	N	0.430328594	None	None	N
A/W	0.986	likely_pathogenic	0.9828	pathogenic	-1.355	Destabilizing	0.958	D	0.798	deleterious	None	None	None	None	N
A/Y	0.9321	likely_pathogenic	0.9216	pathogenic	-0.709	Destabilizing	0.859	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.