TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35159	105700;105701;105702	chr2:178531140;178531139;178531138	chr2:179395867;179395866;179395865
N2AB	33518	100777;100778;100779	chr2:178531140;178531139;178531138	chr2:179395867;179395866;179395865
N2A	32591	97996;97997;97998	chr2:178531140;178531139;178531138	chr2:179395867;179395866;179395865
N2B	26094	78505;78506;78507	chr2:178531140;178531139;178531138	chr2:179395867;179395866;179395865
Novex-1	26219	78880;78881;78882	chr2:178531140;178531139;178531138	chr2:179395867;179395866;179395865
Novex-2	26286	79081;79082;79083	chr2:178531140;178531139;178531138	chr2:179395867;179395866;179395865
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-164
• Domain position: 31
• Structural Position: 45
• Q(SASA): 0.4755
• 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
T/N	rs1468368780	-0.586	0.005	D	0.34	0.126	0.19670166235	gnomAD-2.1.1	4.01E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.86E-06	0
T/N	rs1468368780	-0.586	0.005	D	0.34	0.126	0.19670166235	gnomAD-4.0.0	1.59087E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.8575E-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
T/A	0.0771	likely_benign	0.0788	benign	-0.514	Destabilizing	0.128	N	0.467	neutral	N	0.484073395	None	None	I
T/C	0.4705	ambiguous	0.4725	ambiguous	-0.41	Destabilizing	0.987	D	0.705	prob.neutral	None	None	None	None	I
T/D	0.3307	likely_benign	0.3824	ambiguous	-0.149	Destabilizing	0.32	N	0.623	neutral	None	None	None	None	I
T/E	0.2562	likely_benign	0.2755	benign	-0.182	Destabilizing	0.484	N	0.623	neutral	None	None	None	None	I
T/F	0.2566	likely_benign	0.2876	benign	-0.693	Destabilizing	0.953	D	0.799	deleterious	None	None	None	None	I
T/G	0.2711	likely_benign	0.2948	benign	-0.73	Destabilizing	0.32	N	0.596	neutral	None	None	None	None	I
T/H	0.2359	likely_benign	0.2417	benign	-1.008	Destabilizing	0.925	D	0.779	deleterious	None	None	None	None	I
T/I	0.1693	likely_benign	0.1682	benign	-0.046	Destabilizing	0.834	D	0.733	prob.delet.	N	0.498583252	None	None	I
T/K	0.1709	likely_benign	0.1695	benign	-0.702	Destabilizing	0.32	N	0.631	neutral	None	None	None	None	I
T/L	0.1189	likely_benign	0.1198	benign	-0.046	Destabilizing	0.484	N	0.615	neutral	None	None	None	None	I
T/M	0.1121	likely_benign	0.1109	benign	0.077	Stabilizing	0.987	D	0.703	prob.neutral	None	None	None	None	I
T/N	0.1162	likely_benign	0.1289	benign	-0.556	Destabilizing	0.005	N	0.34	neutral	D	0.533443546	None	None	I
T/P	0.3206	likely_benign	0.4067	ambiguous	-0.17	Destabilizing	0.834	D	0.733	prob.delet.	D	0.523942436	None	None	I
T/Q	0.2158	likely_benign	0.2146	benign	-0.732	Destabilizing	0.767	D	0.738	prob.delet.	None	None	None	None	I
T/R	0.1344	likely_benign	0.138	benign	-0.421	Destabilizing	0.767	D	0.726	prob.delet.	None	None	None	None	I
T/S	0.1042	likely_benign	0.1114	benign	-0.76	Destabilizing	0.027	N	0.37	neutral	N	0.504176645	None	None	I
T/V	0.1359	likely_benign	0.1287	benign	-0.17	Destabilizing	0.656	D	0.521	neutral	None	None	None	None	I
T/W	0.6033	likely_pathogenic	0.6583	pathogenic	-0.68	Destabilizing	0.987	D	0.739	prob.delet.	None	None	None	None	I
T/Y	0.3003	likely_benign	0.3339	benign	-0.438	Destabilizing	0.953	D	0.8	deleterious	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.