TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33780	101563;101564;101565	chr2:178535277;178535276;178535275	chr2:179400004;179400003;179400002
N2AB	32139	96640;96641;96642	chr2:178535277;178535276;178535275	chr2:179400004;179400003;179400002
N2A	31212	93859;93860;93861	chr2:178535277;178535276;178535275	chr2:179400004;179400003;179400002
N2B	24715	74368;74369;74370	chr2:178535277;178535276;178535275	chr2:179400004;179400003;179400002
Novex-1	24840	74743;74744;74745	chr2:178535277;178535276;178535275	chr2:179400004;179400003;179400002
Novex-2	24907	74944;74945;74946	chr2:178535277;178535276;178535275	chr2:179400004;179400003;179400002
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-132
• Domain position: 92
• Structural Position: 127
• Q(SASA): 0.3217
• 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
T/I	rs2154136558	None	None	N	0.355	0.195	0.239901079897	gnomAD-4.0.0	1.36835E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.31863E-05	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
T/A	0.0932	likely_benign	0.0966	benign	-0.902	Destabilizing	0.003	N	0.332	neutral	N	0.45422504	None	None	N
T/C	0.3352	likely_benign	0.3573	ambiguous	-0.45	Destabilizing	0.923	D	0.465	neutral	None	None	None	None	N
T/D	0.8432	likely_pathogenic	0.8718	pathogenic	0.044	Stabilizing	0.495	N	0.52	neutral	None	None	None	None	N
T/E	0.6147	likely_pathogenic	0.6542	pathogenic	0.173	Stabilizing	0.518	D	0.504	neutral	None	None	None	None	N
T/F	0.3464	ambiguous	0.3928	ambiguous	-0.812	Destabilizing	0.664	D	0.543	neutral	None	None	None	None	N
T/G	0.5508	ambiguous	0.5858	pathogenic	-1.261	Destabilizing	0.73	D	0.471	neutral	None	None	None	None	N
T/H	0.4489	ambiguous	0.5333	ambiguous	-1.325	Destabilizing	0.984	D	0.545	neutral	None	None	None	None	N
T/I	0.1054	likely_benign	0.1094	benign	None	Stabilizing	None	N	0.355	neutral	N	0.338880737	None	None	N
T/K	0.4684	ambiguous	0.5292	ambiguous	-0.143	Destabilizing	0.6	D	0.517	neutral	None	None	None	None	N
T/L	0.1278	likely_benign	0.1367	benign	None	Stabilizing	0.028	N	0.33	neutral	None	None	None	None	N
T/M	0.1088	likely_benign	0.11	benign	-0.002	Destabilizing	0.722	D	0.493	neutral	None	None	None	None	N
T/N	0.367	ambiguous	0.4124	ambiguous	-0.535	Destabilizing	0.722	D	0.485	neutral	N	0.484721306	None	None	N
T/P	0.7007	likely_pathogenic	0.7455	pathogenic	-0.268	Destabilizing	0.722	D	0.547	neutral	N	0.484894664	None	None	N
T/Q	0.4087	ambiguous	0.4567	ambiguous	-0.408	Destabilizing	0.882	D	0.495	neutral	None	None	None	None	N
T/R	0.407	ambiguous	0.4607	ambiguous	-0.26	Destabilizing	0.934	D	0.544	neutral	None	None	None	None	N
T/S	0.2326	likely_benign	0.2515	benign	-0.933	Destabilizing	0.032	N	0.384	neutral	N	0.483854514	None	None	N
T/V	0.0824	likely_benign	0.0821	benign	-0.268	Destabilizing	None	N	0.207	neutral	None	None	None	None	N
T/W	0.7948	likely_pathogenic	0.8405	pathogenic	-0.812	Destabilizing	0.994	D	0.617	neutral	None	None	None	None	N
T/Y	0.4387	ambiguous	0.5093	ambiguous	-0.469	Destabilizing	0.934	D	0.562	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.