TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18831	56716;56717;56718	chr2:178599302;178599301;178599300	chr2:179464029;179464028;179464027
N2AB	17190	51793;51794;51795	chr2:178599302;178599301;178599300	chr2:179464029;179464028;179464027
N2A	16263	49012;49013;49014	chr2:178599302;178599301;178599300	chr2:179464029;179464028;179464027
N2B	9766	29521;29522;29523	chr2:178599302;178599301;178599300	chr2:179464029;179464028;179464027
Novex-1	9891	29896;29897;29898	chr2:178599302;178599301;178599300	chr2:179464029;179464028;179464027
Novex-2	9958	30097;30098;30099	chr2:178599302;178599301;178599300	chr2:179464029;179464028;179464027
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: Fn3-24
• Domain position: 48
• Structural Position: 64
• Q(SASA): 0.5818
• Predicted PPI site: I

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/A	None	None	0.64	N	0.403	0.122	0.176091768786	gnomAD-4.0.0	6.86315E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.00763E-07	0	0
T/S	rs778893070	-0.498	0.251	N	0.219	0.12	0.141422826196	gnomAD-2.1.1	4.09E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	9E-06	0
T/S	rs778893070	-0.498	0.251	N	0.219	0.12	0.141422826196	gnomAD-4.0.0	6.86315E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.00763E-07	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	0.0977	likely_benign	0.1013	benign	-0.298	Destabilizing	0.64	D	0.403	neutral	N	0.476074819	None	None	I
T/C	0.4858	ambiguous	0.5081	ambiguous	-0.398	Destabilizing	0.999	D	0.446	neutral	None	None	None	None	I
T/D	0.526	ambiguous	0.497	ambiguous	0.219	Stabilizing	0.976	D	0.378	neutral	None	None	None	None	I
T/E	0.4729	ambiguous	0.4361	ambiguous	0.172	Stabilizing	0.976	D	0.379	neutral	None	None	None	None	I
T/F	0.2722	likely_benign	0.2853	benign	-0.727	Destabilizing	0.976	D	0.523	neutral	None	None	None	None	I
T/G	0.2496	likely_benign	0.2575	benign	-0.442	Destabilizing	0.919	D	0.455	neutral	None	None	None	None	I
T/H	0.3137	likely_benign	0.3224	benign	-0.531	Destabilizing	0.999	D	0.551	neutral	None	None	None	None	I
T/I	0.1906	likely_benign	0.2012	benign	-0.033	Destabilizing	0.938	D	0.379	neutral	N	0.492641782	None	None	I
T/K	0.3659	ambiguous	0.3542	ambiguous	-0.347	Destabilizing	0.968	D	0.37	neutral	N	0.451312447	None	None	I
T/L	0.1145	likely_benign	0.1193	benign	-0.033	Destabilizing	0.034	N	0.289	neutral	None	None	None	None	I
T/M	0.0941	likely_benign	0.1007	benign	-0.207	Destabilizing	0.976	D	0.407	neutral	None	None	None	None	I
T/N	0.1153	likely_benign	0.1262	benign	-0.209	Destabilizing	0.976	D	0.336	neutral	None	None	None	None	I
T/P	0.2762	likely_benign	0.2391	benign	-0.092	Destabilizing	0.984	D	0.405	neutral	N	0.491948348	None	None	I
T/Q	0.296	likely_benign	0.2949	benign	-0.347	Destabilizing	0.988	D	0.392	neutral	None	None	None	None	I
T/R	0.3346	likely_benign	0.3239	benign	-0.054	Destabilizing	0.984	D	0.408	neutral	N	0.447792139	None	None	I
T/S	0.1258	likely_benign	0.1324	benign	-0.416	Destabilizing	0.251	N	0.219	neutral	N	0.430435743	None	None	I
T/V	0.1531	likely_benign	0.154	benign	-0.092	Destabilizing	0.851	D	0.345	neutral	None	None	None	None	I
T/W	0.6471	likely_pathogenic	0.646	pathogenic	-0.793	Destabilizing	0.999	D	0.629	neutral	None	None	None	None	I
T/Y	0.2895	likely_benign	0.2879	benign	-0.488	Destabilizing	0.996	D	0.536	neutral	None	None	None	None	I

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.