TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25759	77500;77501;77502	chr2:178568857;178568856;178568855	chr2:179433584;179433583;179433582
N2AB	24118	72577;72578;72579	chr2:178568857;178568856;178568855	chr2:179433584;179433583;179433582
N2A	23191	69796;69797;69798	chr2:178568857;178568856;178568855	chr2:179433584;179433583;179433582
N2B	16694	50305;50306;50307	chr2:178568857;178568856;178568855	chr2:179433584;179433583;179433582
Novex-1	16819	50680;50681;50682	chr2:178568857;178568856;178568855	chr2:179433584;179433583;179433582
Novex-2	16886	50881;50882;50883	chr2:178568857;178568856;178568855	chr2:179433584;179433583;179433582
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: Fn3-75
• Domain position: 62
• Structural Position: 94
• Q(SASA): 0.5392
• 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/N	rs1399797498	-0.05	0.828	N	0.41	0.199	0.288352970974	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	1.66003E-04
T/N	rs1399797498	-0.05	0.828	N	0.41	0.199	0.288352970974	gnomAD-4.0.0	1.59287E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.0259E-05

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	0.0791	likely_benign	0.0736	benign	-0.585	Destabilizing	0.004	N	0.135	neutral	N	0.473841228	None	None	N
T/C	0.3615	ambiguous	0.2704	benign	-0.34	Destabilizing	0.999	D	0.508	neutral	None	None	None	None	N
T/D	0.316	likely_benign	0.2843	benign	0.155	Stabilizing	0.758	D	0.501	neutral	None	None	None	None	N
T/E	0.2623	likely_benign	0.2559	benign	0.097	Stabilizing	0.84	D	0.422	neutral	None	None	None	None	N
T/F	0.2898	likely_benign	0.246	benign	-0.988	Destabilizing	0.999	D	0.591	neutral	None	None	None	None	N
T/G	0.1605	likely_benign	0.1219	benign	-0.748	Destabilizing	0.963	D	0.476	neutral	None	None	None	None	N
T/H	0.231	likely_benign	0.2036	benign	-1.04	Destabilizing	0.997	D	0.577	neutral	None	None	None	None	N
T/I	0.2116	likely_benign	0.1841	benign	-0.266	Destabilizing	0.987	D	0.529	neutral	D	0.525583706	None	None	N
T/K	0.1843	likely_benign	0.1886	benign	-0.479	Destabilizing	0.88	D	0.45	neutral	None	None	None	None	N
T/L	0.118	likely_benign	0.1045	benign	-0.266	Destabilizing	0.936	D	0.423	neutral	None	None	None	None	N
T/M	0.1201	likely_benign	0.1145	benign	-0.009	Destabilizing	0.997	D	0.519	neutral	None	None	None	None	N
T/N	0.0994	likely_benign	0.088	benign	-0.3	Destabilizing	0.828	D	0.41	neutral	N	0.498165032	None	None	N
T/P	0.0977	likely_benign	0.0776	benign	-0.342	Destabilizing	0.007	N	0.255	neutral	N	0.497434313	None	None	N
T/Q	0.2035	likely_benign	0.2011	benign	-0.518	Destabilizing	0.382	N	0.279	neutral	None	None	None	None	N
T/R	0.1801	likely_benign	0.1915	benign	-0.204	Destabilizing	0.993	D	0.514	neutral	None	None	None	None	N
T/S	0.0868	likely_benign	0.0749	benign	-0.555	Destabilizing	0.137	N	0.371	neutral	N	0.446850777	None	None	N
T/V	0.1562	likely_benign	0.1384	benign	-0.342	Destabilizing	0.913	D	0.331	neutral	None	None	None	None	N
T/W	0.6177	likely_pathogenic	0.525	ambiguous	-0.947	Destabilizing	1.0	D	0.605	neutral	None	None	None	None	N
T/Y	0.2925	likely_benign	0.2282	benign	-0.688	Destabilizing	0.999	D	0.597	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.