TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6548	19867;19868;19869	chr2:178728182;178728181;178728180	chr2:179592909;179592908;179592907
N2AB	6231	18916;18917;18918	chr2:178728182;178728181;178728180	chr2:179592909;179592908;179592907
N2A	5304	16135;16136;16137	chr2:178728182;178728181;178728180	chr2:179592909;179592908;179592907
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: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-49
• Domain position: 68
• Structural Position: 151
• Q(SASA): 0.2672
• 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
T/I	None	None	0.007	N	0.267	0.198	0.453307948783	gnomAD-4.0.0	6.84919E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00114E-07	0	0
T/S	rs369899924	-0.895	0.028	N	0.14	0.078	0.173771789658	gnomAD-2.1.1	8.1E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.79E-05	0
T/S	rs369899924	-0.895	0.028	N	0.14	0.078	0.173771789658	gnomAD-4.0.0	2.05476E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.70034E-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	0.0865	likely_benign	0.0828	benign	-0.932	Destabilizing	0.012	N	0.093	neutral	N	0.417616453	None	None	N
T/C	0.5656	likely_pathogenic	0.5383	ambiguous	-0.627	Destabilizing	0.996	D	0.528	neutral	None	None	None	None	N
T/D	0.505	ambiguous	0.4835	ambiguous	-0.417	Destabilizing	0.59	D	0.528	neutral	None	None	None	None	N
T/E	0.3781	ambiguous	0.3863	ambiguous	-0.392	Destabilizing	0.742	D	0.539	neutral	None	None	None	None	N
T/F	0.4538	ambiguous	0.4591	ambiguous	-0.929	Destabilizing	0.91	D	0.585	neutral	None	None	None	None	N
T/G	0.2863	likely_benign	0.2881	benign	-1.216	Destabilizing	0.373	N	0.502	neutral	None	None	None	None	N
T/H	0.3946	ambiguous	0.3847	ambiguous	-1.453	Destabilizing	0.953	D	0.556	neutral	None	None	None	None	N
T/I	0.3386	likely_benign	0.3753	ambiguous	-0.256	Destabilizing	0.007	N	0.267	neutral	N	0.489682482	None	None	N
T/K	0.2592	likely_benign	0.2544	benign	-0.774	Destabilizing	0.742	D	0.529	neutral	None	None	None	None	N
T/L	0.2	likely_benign	0.2065	benign	-0.256	Destabilizing	0.17	N	0.5	neutral	None	None	None	None	N
T/M	0.1135	likely_benign	0.126	benign	0.045	Stabilizing	0.91	D	0.543	neutral	None	None	None	None	N
T/N	0.1596	likely_benign	0.1578	benign	-0.818	Destabilizing	0.007	N	0.269	neutral	N	0.50733438	None	None	N
T/P	0.4999	ambiguous	0.4355	ambiguous	-0.449	Destabilizing	0.939	D	0.574	neutral	N	0.501203372	None	None	N
T/Q	0.2862	likely_benign	0.3	benign	-0.967	Destabilizing	0.953	D	0.577	neutral	None	None	None	None	N
T/R	0.1831	likely_benign	0.1766	benign	-0.556	Destabilizing	0.91	D	0.575	neutral	None	None	None	None	N
T/S	0.1198	likely_benign	0.1233	benign	-1.121	Destabilizing	0.028	N	0.14	neutral	N	0.417461738	None	None	N
T/V	0.2393	likely_benign	0.2607	benign	-0.449	Destabilizing	0.17	N	0.489	neutral	None	None	None	None	N
T/W	0.8189	likely_pathogenic	0.8185	pathogenic	-0.851	Destabilizing	0.996	D	0.589	neutral	None	None	None	None	N
T/Y	0.4997	ambiguous	0.47	ambiguous	-0.613	Destabilizing	0.953	D	0.583	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.