TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19296	58111;58112;58113	chr2:178594608;178594607;178594606	chr2:179459335;179459334;179459333
N2AB	17655	53188;53189;53190	chr2:178594608;178594607;178594606	chr2:179459335;179459334;179459333
N2A	16728	50407;50408;50409	chr2:178594608;178594607;178594606	chr2:179459335;179459334;179459333
N2B	10231	30916;30917;30918	chr2:178594608;178594607;178594606	chr2:179459335;179459334;179459333
Novex-1	10356	31291;31292;31293	chr2:178594608;178594607;178594606	chr2:179459335;179459334;179459333
Novex-2	10423	31492;31493;31494	chr2:178594608;178594607;178594606	chr2:179459335;179459334;179459333
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-28
• Domain position: 13
• Structural Position: 15
• Q(SASA): 0.1853
• 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
V/I	rs770490179	-0.831	0.014	N	0.208	0.064	0.243972157842	gnomAD-2.1.1	8.09E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.29E-05	None	0	8.93E-06	0
V/I	rs770490179	-0.831	0.014	N	0.208	0.064	0.243972157842	gnomAD-4.0.0	4.78903E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43906E-05	6.06171E-05

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
V/A	0.4161	ambiguous	0.4438	ambiguous	-1.357	Destabilizing	0.822	D	0.457	neutral	N	0.491489775	None	None	N
V/C	0.8005	likely_pathogenic	0.8265	pathogenic	-1.501	Destabilizing	0.998	D	0.711	prob.delet.	None	None	None	None	N
V/D	0.7973	likely_pathogenic	0.8541	pathogenic	-2.029	Highly Destabilizing	0.99	D	0.819	deleterious	N	0.50645534	None	None	N
V/E	0.6148	likely_pathogenic	0.6699	pathogenic	-2.043	Highly Destabilizing	0.993	D	0.766	deleterious	None	None	None	None	N
V/F	0.3776	ambiguous	0.4159	ambiguous	-1.373	Destabilizing	0.942	D	0.743	deleterious	N	0.492745631	None	None	N
V/G	0.5722	likely_pathogenic	0.6197	pathogenic	-1.623	Destabilizing	0.971	D	0.801	deleterious	N	0.507469298	None	None	N
V/H	0.8289	likely_pathogenic	0.8605	pathogenic	-1.242	Destabilizing	0.998	D	0.819	deleterious	None	None	None	None	N
V/I	0.0662	likely_benign	0.069	benign	-0.727	Destabilizing	0.014	N	0.208	neutral	N	0.459163926	None	None	N
V/K	0.5403	ambiguous	0.5748	pathogenic	-1.122	Destabilizing	0.978	D	0.772	deleterious	None	None	None	None	N
V/L	0.3668	ambiguous	0.4077	ambiguous	-0.727	Destabilizing	0.247	N	0.324	neutral	N	0.475878689	None	None	N
V/M	0.2326	likely_benign	0.2445	benign	-0.747	Destabilizing	0.956	D	0.645	neutral	None	None	None	None	N
V/N	0.5609	ambiguous	0.6241	pathogenic	-1.104	Destabilizing	0.993	D	0.817	deleterious	None	None	None	None	N
V/P	0.8584	likely_pathogenic	0.9234	pathogenic	-0.905	Destabilizing	0.993	D	0.785	deleterious	None	None	None	None	N
V/Q	0.587	likely_pathogenic	0.6181	pathogenic	-1.362	Destabilizing	0.993	D	0.785	deleterious	None	None	None	None	N
V/R	0.528	ambiguous	0.5683	pathogenic	-0.654	Destabilizing	0.993	D	0.815	deleterious	None	None	None	None	N
V/S	0.5379	ambiguous	0.5665	pathogenic	-1.521	Destabilizing	0.978	D	0.758	deleterious	None	None	None	None	N
V/T	0.2973	likely_benign	0.3212	benign	-1.433	Destabilizing	0.86	D	0.521	neutral	None	None	None	None	N
V/W	0.9217	likely_pathogenic	0.9389	pathogenic	-1.549	Destabilizing	0.998	D	0.813	deleterious	None	None	None	None	N
V/Y	0.7459	likely_pathogenic	0.7863	pathogenic	-1.186	Destabilizing	0.978	D	0.755	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.