TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35189	105790;105791;105792	chr2:178531050;178531049;178531048	chr2:179395777;179395776;179395775
N2AB	33548	100867;100868;100869	chr2:178531050;178531049;178531048	chr2:179395777;179395776;179395775
N2A	32621	98086;98087;98088	chr2:178531050;178531049;178531048	chr2:179395777;179395776;179395775
N2B	26124	78595;78596;78597	chr2:178531050;178531049;178531048	chr2:179395777;179395776;179395775
Novex-1	26249	78970;78971;78972	chr2:178531050;178531049;178531048	chr2:179395777;179395776;179395775
Novex-2	26316	79171;79172;79173	chr2:178531050;178531049;178531048	chr2:179395777;179395776;179395775
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-164
• Domain position: 61
• Structural Position: 141
• Q(SASA): 0.6301
• 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
S/C	None	None	None	N	0.245	0.32	0.341934017632	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
S/A	0.0811	likely_benign	0.0865	benign	-0.706	Destabilizing	0.012	N	0.262	neutral	D	0.528133727	None	None	N
S/C	0.1632	likely_benign	0.1384	benign	-0.537	Destabilizing	None	N	0.245	neutral	N	0.507688286	None	None	N
S/D	0.387	ambiguous	0.4775	ambiguous	-0.4	Destabilizing	0.038	N	0.281	neutral	None	None	None	None	N
S/E	0.5036	ambiguous	0.5745	pathogenic	-0.452	Destabilizing	0.038	N	0.287	neutral	None	None	None	None	N
S/F	0.1467	likely_benign	0.161	benign	-1.171	Destabilizing	None	N	0.314	neutral	N	0.487760379	None	None	N
S/G	0.1229	likely_benign	0.1264	benign	-0.87	Destabilizing	0.031	N	0.298	neutral	None	None	None	None	N
S/H	0.3074	likely_benign	0.324	benign	-1.378	Destabilizing	0.356	N	0.44	neutral	None	None	None	None	N
S/I	0.1779	likely_benign	0.2062	benign	-0.387	Destabilizing	0.038	N	0.483	neutral	None	None	None	None	N
S/K	0.5966	likely_pathogenic	0.6604	pathogenic	-0.61	Destabilizing	0.038	N	0.28	neutral	None	None	None	None	N
S/L	0.1058	likely_benign	0.1134	benign	-0.387	Destabilizing	0.016	N	0.476	neutral	None	None	None	None	N
S/M	0.2612	likely_benign	0.2761	benign	0.067	Stabilizing	0.356	N	0.439	neutral	None	None	None	None	N
S/N	0.1578	likely_benign	0.1786	benign	-0.492	Destabilizing	0.001	N	0.13	neutral	None	None	None	None	N
S/P	0.1275	likely_benign	0.1872	benign	-0.464	Destabilizing	0.295	N	0.435	neutral	N	0.505566299	None	None	N
S/Q	0.4576	ambiguous	0.5043	ambiguous	-0.821	Destabilizing	0.003	N	0.202	neutral	None	None	None	None	N
S/R	0.4455	ambiguous	0.4943	ambiguous	-0.357	Destabilizing	0.072	N	0.429	neutral	None	None	None	None	N
S/T	0.0852	likely_benign	0.0913	benign	-0.577	Destabilizing	None	N	0.107	neutral	N	0.503083354	None	None	N
S/V	0.1918	likely_benign	0.2152	benign	-0.464	Destabilizing	0.038	N	0.515	neutral	None	None	None	None	N
S/W	0.2939	likely_benign	0.2954	benign	-1.09	Destabilizing	0.676	D	0.517	neutral	None	None	None	None	N
S/Y	0.1657	likely_benign	0.1682	benign	-0.828	Destabilizing	0.093	N	0.509	neutral	D	0.534657055	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.