TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28310	85153;85154;85155	chr2:178561204;178561203;178561202	chr2:179425931;179425930;179425929
N2AB	26669	80230;80231;80232	chr2:178561204;178561203;178561202	chr2:179425931;179425930;179425929
N2A	25742	77449;77450;77451	chr2:178561204;178561203;178561202	chr2:179425931;179425930;179425929
N2B	19245	57958;57959;57960	chr2:178561204;178561203;178561202	chr2:179425931;179425930;179425929
Novex-1	19370	58333;58334;58335	chr2:178561204;178561203;178561202	chr2:179425931;179425930;179425929
Novex-2	19437	58534;58535;58536	chr2:178561204;178561203;178561202	chr2:179425931;179425930;179425929
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-94
• Domain position: 59
• Structural Position: 89
• Q(SASA): 0.17
• 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	rs765062342	0.505	0.994	N	0.777	0.439	0.523082183605	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	2.9E-05	None	0	5.6E-05	None	0	None	0	0	0
T/I	rs765062342	0.505	0.994	N	0.777	0.439	0.523082183605	gnomAD-4.0.0	3.18382E-06	None	None	None	None	N	None	0	2.28686E-05	None	0	2.77824E-05	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
T/A	0.1429	likely_benign	0.1307	benign	-0.621	Destabilizing	0.825	D	0.461	neutral	N	0.501109288	None	None	N
T/C	0.3107	likely_benign	0.3114	benign	-0.405	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
T/D	0.5014	ambiguous	0.4973	ambiguous	-0.756	Destabilizing	0.991	D	0.704	prob.neutral	None	None	None	None	N
T/E	0.4555	ambiguous	0.4125	ambiguous	-0.58	Destabilizing	0.991	D	0.693	prob.neutral	None	None	None	None	N
T/F	0.6001	likely_pathogenic	0.5689	pathogenic	-0.514	Destabilizing	0.995	D	0.799	deleterious	None	None	None	None	N
T/G	0.3167	likely_benign	0.308	benign	-0.996	Destabilizing	0.938	D	0.599	neutral	None	None	None	None	N
T/H	0.4251	ambiguous	0.4055	ambiguous	-1.047	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
T/I	0.4313	ambiguous	0.3919	ambiguous	0.343	Stabilizing	0.994	D	0.777	deleterious	N	0.51484545	None	None	N
T/K	0.3651	ambiguous	0.3415	ambiguous	-0.134	Destabilizing	0.988	D	0.705	prob.neutral	N	0.490905071	None	None	N
T/L	0.1272	likely_benign	0.1175	benign	0.343	Stabilizing	0.968	D	0.579	neutral	None	None	None	None	N
T/M	0.1151	likely_benign	0.1055	benign	0.119	Stabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
T/N	0.0757	likely_benign	0.0722	benign	-0.783	Destabilizing	0.991	D	0.647	neutral	None	None	None	None	N
T/P	0.1303	likely_benign	0.1176	benign	0.053	Stabilizing	0.994	D	0.779	deleterious	N	0.473775095	None	None	N
T/Q	0.3371	likely_benign	0.3097	benign	-0.569	Destabilizing	0.991	D	0.793	deleterious	None	None	None	None	N
T/R	0.2929	likely_benign	0.2712	benign	-0.284	Destabilizing	0.988	D	0.777	deleterious	N	0.478027829	None	None	N
T/S	0.1746	likely_benign	0.1685	benign	-1.025	Destabilizing	0.234	N	0.411	neutral	N	0.50594468	None	None	N
T/V	0.3135	likely_benign	0.2847	benign	0.053	Stabilizing	0.968	D	0.506	neutral	None	None	None	None	N
T/W	0.8615	likely_pathogenic	0.8358	pathogenic	-0.723	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
T/Y	0.482	ambiguous	0.4391	ambiguous	-0.264	Destabilizing	0.998	D	0.797	deleterious	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.