TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30943	93052;93053;93054	chr2:178548799;178548798;178548797	chr2:179413526;179413525;179413524
N2AB	29302	88129;88130;88131	chr2:178548799;178548798;178548797	chr2:179413526;179413525;179413524
N2A	28375	85348;85349;85350	chr2:178548799;178548798;178548797	chr2:179413526;179413525;179413524
N2B	21878	65857;65858;65859	chr2:178548799;178548798;178548797	chr2:179413526;179413525;179413524
Novex-1	22003	66232;66233;66234	chr2:178548799;178548798;178548797	chr2:179413526;179413525;179413524
Novex-2	22070	66433;66434;66435	chr2:178548799;178548798;178548797	chr2:179413526;179413525;179413524
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-150
• Domain position: 17
• Structural Position: 28
• Q(SASA): 0.1961
• 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
I/T	None	None	0.961	N	0.64	0.415	0.547470054201	gnomAD-4.0.0	1.59378E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43271E-05	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
I/A	0.8828	likely_pathogenic	0.8836	pathogenic	-2.422	Highly Destabilizing	0.931	D	0.577	neutral	None	None	None	None	I
I/C	0.9261	likely_pathogenic	0.9266	pathogenic	-1.593	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	I
I/D	0.9986	likely_pathogenic	0.9981	pathogenic	-2.457	Highly Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	I
I/E	0.9959	likely_pathogenic	0.995	pathogenic	-2.306	Highly Destabilizing	0.999	D	0.772	deleterious	None	None	None	None	I
I/F	0.4895	ambiguous	0.4887	ambiguous	-1.52	Destabilizing	0.994	D	0.632	neutral	N	0.497652452	None	None	I
I/G	0.9886	likely_pathogenic	0.9869	pathogenic	-2.908	Highly Destabilizing	0.999	D	0.767	deleterious	None	None	None	None	I
I/H	0.9915	likely_pathogenic	0.9898	pathogenic	-2.227	Highly Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	I
I/K	0.9918	likely_pathogenic	0.9897	pathogenic	-1.928	Destabilizing	0.999	D	0.772	deleterious	None	None	None	None	I
I/L	0.1646	likely_benign	0.1657	benign	-1.056	Destabilizing	0.689	D	0.396	neutral	N	0.424768059	None	None	I
I/M	0.2177	likely_benign	0.2369	benign	-0.829	Destabilizing	0.994	D	0.625	neutral	N	0.457213051	None	None	I
I/N	0.9786	likely_pathogenic	0.9765	pathogenic	-2.011	Highly Destabilizing	0.998	D	0.798	deleterious	N	0.491953531	None	None	I
I/P	0.9935	likely_pathogenic	0.9908	pathogenic	-1.488	Destabilizing	0.999	D	0.797	deleterious	None	None	None	None	I
I/Q	0.9881	likely_pathogenic	0.9863	pathogenic	-2.001	Highly Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	I
I/R	0.9871	likely_pathogenic	0.984	pathogenic	-1.47	Destabilizing	0.999	D	0.8	deleterious	None	None	None	None	I
I/S	0.952	likely_pathogenic	0.9479	pathogenic	-2.678	Highly Destabilizing	0.994	D	0.746	deleterious	N	0.491700041	None	None	I
I/T	0.9309	likely_pathogenic	0.934	pathogenic	-2.387	Highly Destabilizing	0.961	D	0.64	neutral	N	0.479836757	None	None	I
I/V	0.1243	likely_benign	0.1345	benign	-1.488	Destabilizing	0.044	N	0.222	neutral	N	0.426285425	None	None	I
I/W	0.9891	likely_pathogenic	0.9858	pathogenic	-1.801	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	I
I/Y	0.9584	likely_pathogenic	0.9486	pathogenic	-1.555	Destabilizing	0.999	D	0.768	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.