TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7052	21379;21380;21381	chr2:178724105;178724104;178724103	chr2:179588832;179588831;179588830
N2AB	6735	20428;20429;20430	chr2:178724105;178724104;178724103	chr2:179588832;179588831;179588830
N2A	5808	17647;17648;17649	chr2:178724105;178724104;178724103	chr2:179588832;179588831;179588830
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: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-55
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.5722
• 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
N/S	rs1553913467	None	0.001	N	0.167	0.068	0.0846915920261	gnomAD-4.0.0	1.59375E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86328E-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
N/A	0.1911	likely_benign	0.1715	benign	-0.225	Destabilizing	0.002	N	0.205	neutral	None	None	None	None	I
N/C	0.4488	ambiguous	0.3917	ambiguous	0.294	Stabilizing	0.497	N	0.279	neutral	None	None	None	None	I
N/D	0.0627	likely_benign	0.0568	benign	0.03	Stabilizing	None	N	0.021	neutral	N	0.354830758	None	None	I
N/E	0.183	likely_benign	0.1625	benign	-0.024	Destabilizing	None	N	0.025	neutral	None	None	None	None	I
N/F	0.608	likely_pathogenic	0.5593	ambiguous	-0.704	Destabilizing	0.497	N	0.421	neutral	None	None	None	None	I
N/G	0.2448	likely_benign	0.217	benign	-0.36	Destabilizing	None	N	0.025	neutral	None	None	None	None	I
N/H	0.147	likely_benign	0.1353	benign	-0.423	Destabilizing	0.196	N	0.301	neutral	N	0.494209502	None	None	I
N/I	0.2623	likely_benign	0.2484	benign	0.035	Stabilizing	0.065	N	0.421	neutral	N	0.460429055	None	None	I
N/K	0.2352	likely_benign	0.218	benign	0.122	Stabilizing	0.003	N	0.155	neutral	N	0.465329389	None	None	I
N/L	0.314	likely_benign	0.2909	benign	0.035	Stabilizing	0.018	N	0.239	neutral	None	None	None	None	I
N/M	0.3768	ambiguous	0.3539	ambiguous	0.308	Stabilizing	0.497	N	0.293	neutral	None	None	None	None	I
N/P	0.3406	ambiguous	0.309	benign	-0.026	Destabilizing	None	N	0.101	neutral	None	None	None	None	I
N/Q	0.2596	likely_benign	0.2389	benign	-0.351	Destabilizing	None	N	0.037	neutral	None	None	None	None	I
N/R	0.2998	likely_benign	0.2634	benign	0.184	Stabilizing	0.018	N	0.175	neutral	None	None	None	None	I
N/S	0.1056	likely_benign	0.0991	benign	-0.071	Destabilizing	0.001	N	0.167	neutral	N	0.423557338	None	None	I
N/T	0.1506	likely_benign	0.1445	benign	0.003	Stabilizing	0.006	N	0.171	neutral	N	0.457979343	None	None	I
N/V	0.2407	likely_benign	0.2232	benign	-0.026	Destabilizing	0.037	N	0.241	neutral	None	None	None	None	I
N/W	0.7965	likely_pathogenic	0.7614	pathogenic	-0.747	Destabilizing	0.788	D	0.275	neutral	None	None	None	None	I
N/Y	0.1687	likely_benign	0.1689	benign	-0.457	Destabilizing	0.175	N	0.397	neutral	N	0.460682545	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.