TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23105	69538;69539;69540	chr2:178577022;178577021;178577020	chr2:179441749;179441748;179441747
N2AB	21464	64615;64616;64617	chr2:178577022;178577021;178577020	chr2:179441749;179441748;179441747
N2A	20537	61834;61835;61836	chr2:178577022;178577021;178577020	chr2:179441749;179441748;179441747
N2B	14040	42343;42344;42345	chr2:178577022;178577021;178577020	chr2:179441749;179441748;179441747
Novex-1	14165	42718;42719;42720	chr2:178577022;178577021;178577020	chr2:179441749;179441748;179441747
Novex-2	14232	42919;42920;42921	chr2:178577022;178577021;178577020	chr2:179441749;179441748;179441747
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-55
• Domain position: 66
• Structural Position: 98
• Q(SASA): 0.4411
• 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
I/T	rs1430095779	-1.181	0.967	N	0.532	0.378	0.629443713816	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	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
I/A	0.9781	likely_pathogenic	0.9799	pathogenic	-1.564	Destabilizing	0.916	D	0.433	neutral	None	None	None	None	N
I/C	0.9885	likely_pathogenic	0.9884	pathogenic	-0.861	Destabilizing	0.999	D	0.609	neutral	None	None	None	None	N
I/D	0.998	likely_pathogenic	0.9982	pathogenic	-0.961	Destabilizing	0.996	D	0.722	prob.delet.	None	None	None	None	N
I/E	0.9912	likely_pathogenic	0.9915	pathogenic	-0.963	Destabilizing	0.987	D	0.731	prob.delet.	None	None	None	None	N
I/F	0.7154	likely_pathogenic	0.6931	pathogenic	-1.096	Destabilizing	0.967	D	0.544	neutral	N	0.52175118	None	None	N
I/G	0.994	likely_pathogenic	0.9945	pathogenic	-1.879	Destabilizing	0.987	D	0.732	prob.delet.	None	None	None	None	N
I/H	0.9721	likely_pathogenic	0.9698	pathogenic	-0.967	Destabilizing	0.999	D	0.706	prob.neutral	None	None	None	None	N
I/K	0.9694	likely_pathogenic	0.9698	pathogenic	-1.006	Destabilizing	0.987	D	0.731	prob.delet.	None	None	None	None	N
I/L	0.2346	likely_benign	0.2494	benign	-0.779	Destabilizing	0.011	N	0.157	neutral	N	0.451504448	None	None	N
I/M	0.4873	ambiguous	0.4999	ambiguous	-0.582	Destabilizing	0.967	D	0.543	neutral	N	0.484611194	None	None	N
I/N	0.9716	likely_pathogenic	0.9719	pathogenic	-0.812	Destabilizing	0.994	D	0.725	prob.delet.	N	0.498892963	None	None	N
I/P	0.9871	likely_pathogenic	0.9895	pathogenic	-1.009	Destabilizing	0.996	D	0.728	prob.delet.	None	None	None	None	N
I/Q	0.9594	likely_pathogenic	0.9578	pathogenic	-0.996	Destabilizing	0.996	D	0.713	prob.delet.	None	None	None	None	N
I/R	0.9277	likely_pathogenic	0.9314	pathogenic	-0.364	Destabilizing	0.987	D	0.73	prob.delet.	None	None	None	None	N
I/S	0.9693	likely_pathogenic	0.9703	pathogenic	-1.416	Destabilizing	0.983	D	0.637	neutral	N	0.503394706	None	None	N
I/T	0.9771	likely_pathogenic	0.9771	pathogenic	-1.298	Destabilizing	0.967	D	0.532	neutral	N	0.495524584	None	None	N
I/V	0.6459	likely_pathogenic	0.5875	pathogenic	-1.009	Destabilizing	0.426	N	0.323	neutral	N	0.48579038	None	None	N
I/W	0.9719	likely_pathogenic	0.9652	pathogenic	-1.141	Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
I/Y	0.9319	likely_pathogenic	0.9283	pathogenic	-0.93	Destabilizing	0.987	D	0.617	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.