TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31342	94249;94250;94251	chr2:178547602;178547601;178547600	chr2:179412329;179412328;179412327
N2AB	29701	89326;89327;89328	chr2:178547602;178547601;178547600	chr2:179412329;179412328;179412327
N2A	28774	86545;86546;86547	chr2:178547602;178547601;178547600	chr2:179412329;179412328;179412327
N2B	22277	67054;67055;67056	chr2:178547602;178547601;178547600	chr2:179412329;179412328;179412327
Novex-1	22402	67429;67430;67431	chr2:178547602;178547601;178547600	chr2:179412329;179412328;179412327
Novex-2	22469	67630;67631;67632	chr2:178547602;178547601;178547600	chr2:179412329;179412328;179412327
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-116
• Domain position: 35
• Structural Position: 36
• Q(SASA): 0.3613
• 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/I	rs1697759975	None	0.971	N	0.778	0.405	0.48763082235	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/I	rs1697759975	None	0.971	N	0.778	0.405	0.48763082235	gnomAD-4.0.0	6.81647E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.32342E-06	0	0
T/S	None	None	0.058	N	0.181	0.19	0.180583059064	gnomAD-4.0.0	6.84182E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99447E-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	0.2432	likely_benign	0.172	benign	-0.69	Destabilizing	0.489	N	0.474	neutral	N	0.494578829	None	None	I
T/C	0.7468	likely_pathogenic	0.589	pathogenic	-0.433	Destabilizing	0.998	D	0.728	prob.delet.	None	None	None	None	I
T/D	0.831	likely_pathogenic	0.7263	pathogenic	-0.46	Destabilizing	0.956	D	0.698	prob.neutral	None	None	None	None	I
T/E	0.794	likely_pathogenic	0.6957	pathogenic	-0.504	Destabilizing	0.956	D	0.703	prob.neutral	None	None	None	None	I
T/F	0.7476	likely_pathogenic	0.5866	pathogenic	-0.947	Destabilizing	0.978	D	0.798	deleterious	None	None	None	None	I
T/G	0.5039	ambiguous	0.3401	ambiguous	-0.891	Destabilizing	0.754	D	0.607	neutral	None	None	None	None	I
T/H	0.6752	likely_pathogenic	0.5222	ambiguous	-1.231	Destabilizing	0.994	D	0.764	deleterious	None	None	None	None	I
T/I	0.5956	likely_pathogenic	0.4638	ambiguous	-0.259	Destabilizing	0.971	D	0.778	deleterious	N	0.491932493	None	None	I
T/K	0.7127	likely_pathogenic	0.6177	pathogenic	-0.754	Destabilizing	0.915	D	0.703	prob.neutral	None	None	None	None	I
T/L	0.2776	likely_benign	0.1991	benign	-0.259	Destabilizing	0.86	D	0.628	neutral	None	None	None	None	I
T/M	0.21	likely_benign	0.1633	benign	0.162	Stabilizing	0.998	D	0.729	prob.delet.	None	None	None	None	I
T/N	0.3039	likely_benign	0.2114	benign	-0.615	Destabilizing	0.89	D	0.671	neutral	D	0.523178119	None	None	I
T/P	0.7136	likely_pathogenic	0.6326	pathogenic	-0.372	Destabilizing	0.971	D	0.778	deleterious	D	0.525813816	None	None	I
T/Q	0.589	likely_pathogenic	0.4742	ambiguous	-0.904	Destabilizing	0.956	D	0.771	deleterious	None	None	None	None	I
T/R	0.6513	likely_pathogenic	0.5411	ambiguous	-0.403	Destabilizing	0.956	D	0.785	deleterious	None	None	None	None	I
T/S	0.1897	likely_benign	0.1246	benign	-0.828	Destabilizing	0.058	N	0.181	neutral	N	0.515673357	None	None	I
T/V	0.4597	ambiguous	0.3481	ambiguous	-0.372	Destabilizing	0.86	D	0.587	neutral	None	None	None	None	I
T/W	0.9188	likely_pathogenic	0.8399	pathogenic	-0.875	Destabilizing	0.998	D	0.791	deleterious	None	None	None	None	I
T/Y	0.7718	likely_pathogenic	0.6185	pathogenic	-0.644	Destabilizing	0.993	D	0.79	deleterious	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.