TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15360	46303;46304;46305	chr2:178620443;178620442;178620441	chr2:179485170;179485169;179485168
N2AB	13719	41380;41381;41382	chr2:178620443;178620442;178620441	chr2:179485170;179485169;179485168
N2A	12792	38599;38600;38601	chr2:178620443;178620442;178620441	chr2:179485170;179485169;179485168
N2B	6295	19108;19109;19110	chr2:178620443;178620442;178620441	chr2:179485170;179485169;179485168
Novex-1	6420	19483;19484;19485	chr2:178620443;178620442;178620441	chr2:179485170;179485169;179485168
Novex-2	6487	19684;19685;19686	chr2:178620443;178620442;178620441	chr2:179485170;179485169;179485168
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-105
• Domain position: 59
• Structural Position: 140
• Q(SASA): 0.1071
• 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	rs746352388	-1.467	0.998	D	0.685	0.614	0.666064869456	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.94E-06	0
I/M	rs746352388	-1.467	0.998	D	0.685	0.614	0.666064869456	gnomAD-4.0.0	3.18877E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72849E-06	0	0
I/T	rs1465320800	-3.013	0.989	D	0.755	0.76	0.844994757482	gnomAD-2.1.1	1.43E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	3.14E-05	0
I/T	rs1465320800	-3.013	0.989	D	0.755	0.76	0.844994757482	gnomAD-3.1.2	1.98E-05	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	0	2.95E-05	0	0
I/T	rs1465320800	-3.013	0.989	D	0.755	0.76	0.844994757482	gnomAD-4.0.0	1.92282E-05	None	None	None	None	N	None	1.33711E-05	0	None	0	0	None	0	0	2.54473E-05	0	0
I/V	rs758542642	-1.454	0.333	D	0.263	0.425	0.717905595574	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	2.91E-05	None	0	0	None	0	None	0	0	0
I/V	rs758542642	-1.454	0.333	D	0.263	0.425	0.717905595574	gnomAD-4.0.0	1.59436E-06	None	None	None	None	N	None	0	2.29085E-05	None	0	0	None	0	0	0	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	0.9652	likely_pathogenic	0.9668	pathogenic	-3.056	Highly Destabilizing	0.992	D	0.686	prob.neutral	None	None	None	None	N
I/C	0.9777	likely_pathogenic	0.982	pathogenic	-2.843	Highly Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
I/D	0.9987	likely_pathogenic	0.9985	pathogenic	-3.528	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
I/E	0.9935	likely_pathogenic	0.9922	pathogenic	-3.26	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
I/F	0.6647	likely_pathogenic	0.6949	pathogenic	-1.913	Destabilizing	0.998	D	0.727	prob.delet.	D	0.738147982	None	None	N
I/G	0.9953	likely_pathogenic	0.9955	pathogenic	-3.657	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
I/H	0.9902	likely_pathogenic	0.9903	pathogenic	-3.106	Highly Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
I/K	0.9807	likely_pathogenic	0.9804	pathogenic	-2.545	Highly Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
I/L	0.3331	likely_benign	0.3472	ambiguous	-1.285	Destabilizing	0.889	D	0.401	neutral	D	0.604315515	None	None	N
I/M	0.3937	ambiguous	0.4058	ambiguous	-1.507	Destabilizing	0.998	D	0.685	prob.neutral	D	0.679476999	None	None	N
I/N	0.9805	likely_pathogenic	0.9785	pathogenic	-3.049	Highly Destabilizing	0.999	D	0.859	deleterious	D	0.736612995	None	None	N
I/P	0.9981	likely_pathogenic	0.9979	pathogenic	-1.86	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
I/Q	0.9842	likely_pathogenic	0.9838	pathogenic	-2.84	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
I/R	0.9717	likely_pathogenic	0.9707	pathogenic	-2.272	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
I/S	0.9759	likely_pathogenic	0.9746	pathogenic	-3.794	Highly Destabilizing	0.998	D	0.831	deleterious	D	0.736612995	None	None	N
I/T	0.9687	likely_pathogenic	0.9693	pathogenic	-3.359	Highly Destabilizing	0.989	D	0.755	deleterious	D	0.736799314	None	None	N
I/V	0.1462	likely_benign	0.1558	benign	-1.86	Destabilizing	0.333	N	0.263	neutral	D	0.644070135	None	None	N
I/W	0.9874	likely_pathogenic	0.9903	pathogenic	-2.281	Highly Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
I/Y	0.9592	likely_pathogenic	0.9612	pathogenic	-2.071	Highly Destabilizing	1.0	D	0.749	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.