TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19298	58117;58118;58119	chr2:178594602;178594601;178594600	chr2:179459329;179459328;179459327
N2AB	17657	53194;53195;53196	chr2:178594602;178594601;178594600	chr2:179459329;179459328;179459327
N2A	16730	50413;50414;50415	chr2:178594602;178594601;178594600	chr2:179459329;179459328;179459327
N2B	10233	30922;30923;30924	chr2:178594602;178594601;178594600	chr2:179459329;179459328;179459327
Novex-1	10358	31297;31298;31299	chr2:178594602;178594601;178594600	chr2:179459329;179459328;179459327
Novex-2	10425	31498;31499;31500	chr2:178594602;178594601;178594600	chr2:179459329;179459328;179459327
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-28
• Domain position: 15
• Structural Position: 17
• Q(SASA): 0.3628
• 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
K/Q	rs781725039	-0.564	0.204	N	0.257	0.215	0.208000267992	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	0	None	0	2.2414E-04	None	0	None	0	0	0
K/Q	rs781725039	-0.564	0.204	N	0.257	0.215	0.208000267992	gnomAD-4.0.0	3.50909E-05	None	None	None	None	N	None	0	0	None	0	6.11723E-04	None	0	0	0	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
K/A	0.3794	ambiguous	0.4232	ambiguous	-0.129	Destabilizing	0.845	D	0.569	neutral	None	None	None	None	N
K/C	0.7579	likely_pathogenic	0.7798	pathogenic	-0.126	Destabilizing	0.999	D	0.777	deleterious	None	None	None	None	N
K/D	0.7805	likely_pathogenic	0.8143	pathogenic	-0.39	Destabilizing	0.845	D	0.597	neutral	None	None	None	None	N
K/E	0.3241	likely_benign	0.3684	ambiguous	-0.384	Destabilizing	0.805	D	0.545	neutral	N	0.495524584	None	None	N
K/F	0.9587	likely_pathogenic	0.9653	pathogenic	-0.436	Destabilizing	0.996	D	0.738	prob.delet.	None	None	None	None	N
K/G	0.5234	ambiguous	0.5708	pathogenic	-0.366	Destabilizing	0.916	D	0.612	neutral	None	None	None	None	N
K/H	0.5309	ambiguous	0.5618	ambiguous	-0.887	Destabilizing	0.987	D	0.638	neutral	None	None	None	None	N
K/I	0.7376	likely_pathogenic	0.7727	pathogenic	0.429	Stabilizing	0.983	D	0.743	deleterious	N	0.489246003	None	None	N
K/L	0.6854	likely_pathogenic	0.7212	pathogenic	0.429	Stabilizing	0.975	D	0.619	neutral	None	None	None	None	N
K/M	0.5059	ambiguous	0.5547	ambiguous	0.618	Stabilizing	0.997	D	0.617	neutral	None	None	None	None	N
K/N	0.5852	likely_pathogenic	0.6265	pathogenic	0.093	Stabilizing	0.204	N	0.291	neutral	N	0.483347508	None	None	N
K/P	0.8143	likely_pathogenic	0.8247	pathogenic	0.272	Stabilizing	0.987	D	0.634	neutral	None	None	None	None	N
K/Q	0.1949	likely_benign	0.2118	benign	-0.228	Destabilizing	0.204	N	0.257	neutral	N	0.518518874	None	None	N
K/R	0.0766	likely_benign	0.0786	benign	-0.039	Destabilizing	0.805	D	0.521	neutral	N	0.451987238	None	None	N
K/S	0.4931	ambiguous	0.5416	ambiguous	-0.39	Destabilizing	0.916	D	0.543	neutral	None	None	None	None	N
K/T	0.4253	ambiguous	0.477	ambiguous	-0.232	Destabilizing	0.892	D	0.599	neutral	N	0.521441749	None	None	N
K/V	0.6288	likely_pathogenic	0.6752	pathogenic	0.272	Stabilizing	0.975	D	0.601	neutral	None	None	None	None	N
K/W	0.937	likely_pathogenic	0.9414	pathogenic	-0.392	Destabilizing	0.999	D	0.764	deleterious	None	None	None	None	N
K/Y	0.8795	likely_pathogenic	0.8901	pathogenic	0.004	Stabilizing	0.996	D	0.723	prob.delet.	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.