TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21565	64918;64919;64920	chr2:178584948;178584947;178584946	chr2:179449675;179449674;179449673
N2AB	19924	59995;59996;59997	chr2:178584948;178584947;178584946	chr2:179449675;179449674;179449673
N2A	18997	57214;57215;57216	chr2:178584948;178584947;178584946	chr2:179449675;179449674;179449673
N2B	12500	37723;37724;37725	chr2:178584948;178584947;178584946	chr2:179449675;179449674;179449673
Novex-1	12625	38098;38099;38100	chr2:178584948;178584947;178584946	chr2:179449675;179449674;179449673
Novex-2	12692	38299;38300;38301	chr2:178584948;178584947;178584946	chr2:179449675;179449674;179449673
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-44
• Domain position: 7
• Structural Position: 7
• Q(SASA): 0.1196
• 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
P/T	rs780636947	-2.37	0.92	N	0.601	0.268	0.245101548738	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	6.59E-05	0	None	0	0	None	0	None	0	0	0
P/T	rs780636947	-2.37	0.92	N	0.601	0.268	0.245101548738	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	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
P/A	0.0919	likely_benign	0.0828	benign	-1.086	Destabilizing	0.061	N	0.293	neutral	N	0.447338274	None	None	N
P/C	0.5898	likely_pathogenic	0.5102	ambiguous	-0.574	Destabilizing	0.999	D	0.649	neutral	None	None	None	None	N
P/D	0.5594	ambiguous	0.4991	ambiguous	-1.214	Destabilizing	0.969	D	0.605	neutral	None	None	None	None	N
P/E	0.3422	ambiguous	0.298	benign	-1.277	Destabilizing	0.969	D	0.611	neutral	None	None	None	None	N
P/F	0.5418	ambiguous	0.4689	ambiguous	-1.036	Destabilizing	0.997	D	0.665	neutral	None	None	None	None	N
P/G	0.2928	likely_benign	0.2455	benign	-1.309	Destabilizing	0.02	N	0.367	neutral	None	None	None	None	N
P/H	0.2919	likely_benign	0.2537	benign	-0.873	Destabilizing	0.999	D	0.594	neutral	N	0.472884543	None	None	N
P/I	0.4096	ambiguous	0.3713	ambiguous	-0.601	Destabilizing	0.991	D	0.663	neutral	None	None	None	None	N
P/K	0.3326	likely_benign	0.295	benign	-1.035	Destabilizing	0.969	D	0.602	neutral	None	None	None	None	N
P/L	0.163	likely_benign	0.145	benign	-0.601	Destabilizing	0.92	D	0.675	prob.neutral	N	0.476758884	None	None	N
P/M	0.355	ambiguous	0.3091	benign	-0.406	Destabilizing	0.999	D	0.595	neutral	None	None	None	None	N
P/N	0.4498	ambiguous	0.381	ambiguous	-0.69	Destabilizing	0.991	D	0.635	neutral	None	None	None	None	N
P/Q	0.2077	likely_benign	0.1817	benign	-0.938	Destabilizing	0.997	D	0.609	neutral	None	None	None	None	N
P/R	0.2754	likely_benign	0.2465	benign	-0.41	Destabilizing	0.988	D	0.623	neutral	N	0.45376633	None	None	N
P/S	0.164	likely_benign	0.1417	benign	-1.023	Destabilizing	0.852	D	0.531	neutral	N	0.498804458	None	None	N
P/T	0.1919	likely_benign	0.1706	benign	-0.995	Destabilizing	0.92	D	0.601	neutral	N	0.45401982	None	None	N
P/V	0.2928	likely_benign	0.2658	benign	-0.728	Destabilizing	0.939	D	0.63	neutral	None	None	None	None	N
P/W	0.7682	likely_pathogenic	0.7171	pathogenic	-1.18	Destabilizing	0.999	D	0.695	prob.neutral	None	None	None	None	N
P/Y	0.4609	ambiguous	0.3939	ambiguous	-0.916	Destabilizing	0.997	D	0.662	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.