TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1517	4774;4775;4776	chr2:178777516;178777515;178777514	chr2:179642243;179642242;179642241
N2AB	1517	4774;4775;4776	chr2:178777516;178777515;178777514	chr2:179642243;179642242;179642241
N2A	1517	4774;4775;4776	chr2:178777516;178777515;178777514	chr2:179642243;179642242;179642241
N2B	1471	4636;4637;4638	chr2:178777516;178777515;178777514	chr2:179642243;179642242;179642241
Novex-1	1471	4636;4637;4638	chr2:178777516;178777515;178777514	chr2:179642243;179642242;179642241
Novex-2	1471	4636;4637;4638	chr2:178777516;178777515;178777514	chr2:179642243;179642242;179642241
Novex-3	1517	4774;4775;4776	chr2:178777516;178777515;178777514	chr2:179642243;179642242;179642241

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-6
• Domain position: 61
• Structural Position: 140
• Q(SASA): 0.0918
• 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
I/M	rs1438474327	-1.373	0.997	D	0.697	0.62	0.701978191309	gnomAD-2.1.1	3.18E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
I/M	rs1438474327	-1.373	0.997	D	0.697	0.62	0.701978191309	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
I/M	rs1438474327	-1.373	0.997	D	0.697	0.62	0.701978191309	gnomAD-4.0.0	2.02973E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.40978E-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
I/A	0.937	likely_pathogenic	0.9456	pathogenic	-3.046	Highly Destabilizing	0.983	D	0.703	prob.neutral	None	None	None	None	N
I/C	0.9784	likely_pathogenic	0.9804	pathogenic	-2.467	Highly Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
I/D	0.9994	likely_pathogenic	0.9994	pathogenic	-3.788	Highly Destabilizing	0.999	D	0.863	deleterious	None	None	None	None	N
I/E	0.9979	likely_pathogenic	0.9981	pathogenic	-3.536	Highly Destabilizing	0.999	D	0.871	deleterious	None	None	None	None	N
I/F	0.7303	likely_pathogenic	0.7515	pathogenic	-1.803	Destabilizing	0.997	D	0.733	prob.delet.	D	0.584529973	None	None	N
I/G	0.9971	likely_pathogenic	0.9975	pathogenic	-3.616	Highly Destabilizing	0.999	D	0.874	deleterious	None	None	None	None	N
I/H	0.9954	likely_pathogenic	0.9957	pathogenic	-3.082	Highly Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
I/K	0.9937	likely_pathogenic	0.994	pathogenic	-2.578	Highly Destabilizing	0.999	D	0.869	deleterious	None	None	None	None	N
I/L	0.3805	ambiguous	0.3905	ambiguous	-1.365	Destabilizing	0.798	D	0.437	neutral	D	0.538458889	None	None	N
I/M	0.3972	ambiguous	0.4336	ambiguous	-1.382	Destabilizing	0.997	D	0.697	prob.neutral	D	0.676736983	None	None	N
I/N	0.9893	likely_pathogenic	0.9913	pathogenic	-3.047	Highly Destabilizing	0.999	D	0.869	deleterious	D	0.732582044	None	None	N
I/P	0.9985	likely_pathogenic	0.9986	pathogenic	-1.912	Destabilizing	0.999	D	0.863	deleterious	None	None	None	None	N
I/Q	0.9951	likely_pathogenic	0.9954	pathogenic	-2.867	Highly Destabilizing	0.999	D	0.877	deleterious	None	None	None	None	N
I/R	0.9886	likely_pathogenic	0.9892	pathogenic	-2.228	Highly Destabilizing	0.999	D	0.875	deleterious	None	None	None	None	N
I/S	0.973	likely_pathogenic	0.9773	pathogenic	-3.688	Highly Destabilizing	0.997	D	0.841	deleterious	D	0.790051282	None	None	N
I/T	0.8732	likely_pathogenic	0.8952	pathogenic	-3.293	Highly Destabilizing	0.978	D	0.771	deleterious	D	0.695907722	None	None	N
I/V	0.1299	likely_benign	0.1366	benign	-1.912	Destabilizing	0.198	N	0.287	neutral	D	0.543679767	None	None	N
I/W	0.9948	likely_pathogenic	0.995	pathogenic	-2.288	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
I/Y	0.9847	likely_pathogenic	0.9856	pathogenic	-2.074	Highly Destabilizing	0.999	D	0.769	deleterious	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.