TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24539	73840;73841;73842	chr2:178572517;178572516;178572515	chr2:179437244;179437243;179437242
N2AB	22898	68917;68918;68919	chr2:178572517;178572516;178572515	chr2:179437244;179437243;179437242
N2A	21971	66136;66137;66138	chr2:178572517;178572516;178572515	chr2:179437244;179437243;179437242
N2B	15474	46645;46646;46647	chr2:178572517;178572516;178572515	chr2:179437244;179437243;179437242
Novex-1	15599	47020;47021;47022	chr2:178572517;178572516;178572515	chr2:179437244;179437243;179437242
Novex-2	15666	47221;47222;47223	chr2:178572517;178572516;178572515	chr2:179437244;179437243;179437242
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: Fn3-66
• Domain position: 21
• Structural Position: 23
• Q(SASA): 0.2151
• 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/R	rs890303676	-0.664	0.989	D	0.532	0.327	0.346544149963	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
T/R	rs890303676	-0.664	0.989	D	0.532	0.327	0.346544149963	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/R	rs890303676	-0.664	0.989	D	0.532	0.327	0.346544149963	gnomAD-4.0.0	3.84515E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.18202E-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
T/A	0.0792	likely_benign	0.0784	benign	-1.199	Destabilizing	0.123	N	0.292	neutral	N	0.484638374	None	None	N
T/C	0.1968	likely_benign	0.2046	benign	-0.899	Destabilizing	0.999	D	0.546	neutral	None	None	None	None	N
T/D	0.5662	likely_pathogenic	0.5096	ambiguous	-1.401	Destabilizing	0.734	D	0.475	neutral	None	None	None	None	N
T/E	0.4462	ambiguous	0.4051	ambiguous	-1.236	Destabilizing	0.902	D	0.469	neutral	None	None	None	None	N
T/F	0.1501	likely_benign	0.1439	benign	-0.903	Destabilizing	0.996	D	0.607	neutral	None	None	None	None	N
T/G	0.186	likely_benign	0.1838	benign	-1.589	Destabilizing	0.921	D	0.509	neutral	None	None	None	None	N
T/H	0.2151	likely_benign	0.2105	benign	-1.714	Destabilizing	0.999	D	0.631	neutral	None	None	None	None	N
T/I	0.101	likely_benign	0.0999	benign	-0.188	Destabilizing	0.115	N	0.396	neutral	N	0.468725893	None	None	N
T/K	0.349	ambiguous	0.3246	benign	-0.665	Destabilizing	0.907	D	0.464	neutral	D	0.523887408	None	None	N
T/L	0.0668	likely_benign	0.0667	benign	-0.188	Destabilizing	0.727	D	0.427	neutral	None	None	None	None	N
T/M	0.07	likely_benign	0.0728	benign	-0.131	Destabilizing	0.989	D	0.55	neutral	None	None	None	None	N
T/N	0.1263	likely_benign	0.1233	benign	-1.22	Destabilizing	0.734	D	0.456	neutral	None	None	None	None	N
T/P	0.7916	likely_pathogenic	0.7211	pathogenic	-0.494	Destabilizing	0.937	D	0.535	neutral	D	0.526330341	None	None	N
T/Q	0.2319	likely_benign	0.2272	benign	-1.099	Destabilizing	0.955	D	0.531	neutral	None	None	None	None	N
T/R	0.2952	likely_benign	0.2588	benign	-0.755	Destabilizing	0.989	D	0.532	neutral	D	0.523367333	None	None	N
T/S	0.0798	likely_benign	0.0799	benign	-1.457	Destabilizing	0.004	N	0.174	neutral	N	0.424392418	None	None	N
T/V	0.0868	likely_benign	0.0895	benign	-0.494	Destabilizing	0.049	N	0.161	neutral	None	None	None	None	N
T/W	0.5195	ambiguous	0.5003	ambiguous	-0.993	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	N
T/Y	0.2193	likely_benign	0.2117	benign	-0.646	Destabilizing	0.999	D	0.609	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.