TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14731	44416;44417;44418	chr2:178630331;178630330;178630329	chr2:179495058;179495057;179495056
N2AB	13090	39493;39494;39495	chr2:178630331;178630330;178630329	chr2:179495058;179495057;179495056
N2A	12163	36712;36713;36714	chr2:178630331;178630330;178630329	chr2:179495058;179495057;179495056
N2B	5666	17221;17222;17223	chr2:178630331;178630330;178630329	chr2:179495058;179495057;179495056
Novex-1	5791	17596;17597;17598	chr2:178630331;178630330;178630329	chr2:179495058;179495057;179495056
Novex-2	5858	17797;17798;17799	chr2:178630331;178630330;178630329	chr2:179495058;179495057;179495056
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-98
• Domain position: 57
• Structural Position: 138
• Q(SASA): 0.0876
• 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
L/F	rs771361227	-1.643	0.999	D	0.82	0.593	0.785219713586	gnomAD-2.1.1	1.13242E-04	None	None	None	None	N	None	0	0	None	0	0	None	9.30356E-04	None	0	0	0
L/F	rs771361227	-1.643	0.999	D	0.82	0.593	0.785219713586	gnomAD-3.1.2	4.6E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	1.45228E-03	0
L/F	rs771361227	-1.643	0.999	D	0.82	0.593	0.785219713586	gnomAD-4.0.0	6.45231E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.48031E-07	1.09363E-03	6.4119E-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
L/A	0.9331	likely_pathogenic	0.9004	pathogenic	-2.498	Highly Destabilizing	0.998	D	0.731	deleterious	None	None	None	None	N
L/C	0.9022	likely_pathogenic	0.901	pathogenic	-1.704	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
L/D	0.9998	likely_pathogenic	0.9997	pathogenic	-3.243	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
L/E	0.9979	likely_pathogenic	0.9971	pathogenic	-2.932	Highly Destabilizing	0.999	D	0.842	deleterious	None	None	None	None	N
L/F	0.7995	likely_pathogenic	0.7713	pathogenic	-1.563	Destabilizing	0.999	D	0.82	deleterious	D	0.713871158	None	None	N
L/G	0.992	likely_pathogenic	0.9897	pathogenic	-3.097	Highly Destabilizing	0.999	D	0.826	deleterious	None	None	None	None	N
L/H	0.9933	likely_pathogenic	0.9918	pathogenic	-2.782	Highly Destabilizing	1.0	D	0.837	deleterious	D	0.717633638	None	None	N
L/I	0.3271	likely_benign	0.2603	benign	-0.713	Destabilizing	0.997	D	0.58	neutral	D	0.711943723	None	None	N
L/K	0.9946	likely_pathogenic	0.9936	pathogenic	-2.017	Highly Destabilizing	0.999	D	0.86	deleterious	None	None	None	None	N
L/M	0.4976	ambiguous	0.4473	ambiguous	-0.725	Destabilizing	0.999	D	0.779	deleterious	None	None	None	None	N
L/N	0.9979	likely_pathogenic	0.9976	pathogenic	-2.691	Highly Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
L/P	0.998	likely_pathogenic	0.9974	pathogenic	-1.296	Destabilizing	1.0	D	0.864	deleterious	D	0.717633638	None	None	N
L/Q	0.9898	likely_pathogenic	0.9866	pathogenic	-2.369	Highly Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
L/R	0.9844	likely_pathogenic	0.9806	pathogenic	-2.044	Highly Destabilizing	0.999	D	0.856	deleterious	D	0.717633638	None	None	N
L/S	0.9954	likely_pathogenic	0.9924	pathogenic	-3.274	Highly Destabilizing	0.999	D	0.864	deleterious	None	None	None	None	N
L/T	0.9782	likely_pathogenic	0.9619	pathogenic	-2.795	Highly Destabilizing	0.999	D	0.811	deleterious	None	None	None	None	N
L/V	0.3325	likely_benign	0.2287	benign	-1.296	Destabilizing	0.997	D	0.582	neutral	D	0.714614901	None	None	N
L/W	0.9848	likely_pathogenic	0.9814	pathogenic	-2.01	Highly Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
L/Y	0.9865	likely_pathogenic	0.9867	pathogenic	-1.698	Destabilizing	0.999	D	0.817	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.