TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18836	56731;56732;56733	chr2:178599287;178599286;178599285	chr2:179464014;179464013;179464012
N2AB	17195	51808;51809;51810	chr2:178599287;178599286;178599285	chr2:179464014;179464013;179464012
N2A	16268	49027;49028;49029	chr2:178599287;178599286;178599285	chr2:179464014;179464013;179464012
N2B	9771	29536;29537;29538	chr2:178599287;178599286;178599285	chr2:179464014;179464013;179464012
Novex-1	9896	29911;29912;29913	chr2:178599287;178599286;178599285	chr2:179464014;179464013;179464012
Novex-2	9963	30112;30113;30114	chr2:178599287;178599286;178599285	chr2:179464014;179464013;179464012
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Fn3-24
• Domain position: 53
• Structural Position: 69
• Q(SASA): 0.1532
• 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
S/F	None	None	0.896	N	0.5	0.42	0.623559015015	gnomAD-4.0.0	1.61964E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8881E-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
S/A	0.1104	likely_benign	0.0941	benign	-0.59	Destabilizing	0.007	N	0.141	neutral	N	0.457126486	None	None	N
S/C	0.1272	likely_benign	0.1097	benign	-0.378	Destabilizing	0.009	N	0.231	neutral	N	0.480273236	None	None	N
S/D	0.6486	likely_pathogenic	0.5242	ambiguous	-0.626	Destabilizing	0.617	D	0.481	neutral	None	None	None	None	N
S/E	0.819	likely_pathogenic	0.6853	pathogenic	-0.528	Destabilizing	0.617	D	0.431	neutral	None	None	None	None	N
S/F	0.451	ambiguous	0.3276	benign	-0.62	Destabilizing	0.896	D	0.5	neutral	N	0.482791223	None	None	N
S/G	0.1591	likely_benign	0.1298	benign	-0.934	Destabilizing	0.4	N	0.415	neutral	None	None	None	None	N
S/H	0.5919	likely_pathogenic	0.4671	ambiguous	-1.439	Destabilizing	0.992	D	0.447	neutral	None	None	None	None	N
S/I	0.3492	ambiguous	0.2629	benign	0.241	Stabilizing	0.447	N	0.455	neutral	None	None	None	None	N
S/K	0.8975	likely_pathogenic	0.7791	pathogenic	-0.517	Destabilizing	0.617	D	0.429	neutral	None	None	None	None	N
S/L	0.1901	likely_benign	0.1443	benign	0.241	Stabilizing	0.447	N	0.418	neutral	None	None	None	None	N
S/M	0.3261	likely_benign	0.2357	benign	0.29	Stabilizing	0.92	D	0.464	neutral	None	None	None	None	N
S/N	0.3055	likely_benign	0.224	benign	-0.858	Destabilizing	0.617	D	0.479	neutral	None	None	None	None	N
S/P	0.7671	likely_pathogenic	0.637	pathogenic	0.001	Stabilizing	0.896	D	0.457	neutral	N	0.508478026	None	None	N
S/Q	0.7609	likely_pathogenic	0.6316	pathogenic	-0.746	Destabilizing	0.92	D	0.513	neutral	None	None	None	None	N
S/R	0.8574	likely_pathogenic	0.7314	pathogenic	-0.69	Destabilizing	0.85	D	0.462	neutral	None	None	None	None	N
S/T	0.0745	likely_benign	0.0627	benign	-0.653	Destabilizing	0.002	N	0.133	neutral	N	0.454987471	None	None	N
S/V	0.2954	likely_benign	0.2221	benign	0.001	Stabilizing	0.447	N	0.409	neutral	None	None	None	None	N
S/W	0.6216	likely_pathogenic	0.4963	ambiguous	-0.797	Destabilizing	0.992	D	0.555	neutral	None	None	None	None	N
S/Y	0.4253	ambiguous	0.3119	benign	-0.409	Destabilizing	0.963	D	0.507	neutral	N	0.500647976	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.