TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25758	77497;77498;77499	chr2:178568860;178568859;178568858	chr2:179433587;179433586;179433585
N2AB	24117	72574;72575;72576	chr2:178568860;178568859;178568858	chr2:179433587;179433586;179433585
N2A	23190	69793;69794;69795	chr2:178568860;178568859;178568858	chr2:179433587;179433586;179433585
N2B	16693	50302;50303;50304	chr2:178568860;178568859;178568858	chr2:179433587;179433586;179433585
Novex-1	16818	50677;50678;50679	chr2:178568860;178568859;178568858	chr2:179433587;179433586;179433585
Novex-2	16885	50878;50879;50880	chr2:178568860;178568859;178568858	chr2:179433587;179433586;179433585
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: Fn3-75
• Domain position: 61
• Structural Position: 93
• Q(SASA): 0.1642
• 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/V	None	None	0.002	N	0.2	0.071	0.345175991111	gnomAD-4.0.0	2.40065E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62501E-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	0.8913	likely_pathogenic	0.862	pathogenic	-2.369	Highly Destabilizing	0.963	D	0.733	prob.delet.	None	None	None	None	N
I/C	0.9184	likely_pathogenic	0.8885	pathogenic	-1.755	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
I/D	0.9967	likely_pathogenic	0.9956	pathogenic	-1.942	Destabilizing	0.999	D	0.842	deleterious	None	None	None	None	N
I/E	0.989	likely_pathogenic	0.9863	pathogenic	-1.766	Destabilizing	0.996	D	0.843	deleterious	None	None	None	None	N
I/F	0.5748	likely_pathogenic	0.4923	ambiguous	-1.441	Destabilizing	0.102	N	0.437	neutral	N	0.488347404	None	None	N
I/G	0.9854	likely_pathogenic	0.9819	pathogenic	-2.881	Highly Destabilizing	0.997	D	0.831	deleterious	None	None	None	None	N
I/H	0.9812	likely_pathogenic	0.975	pathogenic	-2.109	Highly Destabilizing	0.999	D	0.842	deleterious	None	None	None	None	N
I/K	0.9788	likely_pathogenic	0.9723	pathogenic	-1.782	Destabilizing	0.917	D	0.845	deleterious	None	None	None	None	N
I/L	0.2993	likely_benign	0.2558	benign	-0.928	Destabilizing	0.095	N	0.499	neutral	N	0.462545374	None	None	N
I/M	0.3497	ambiguous	0.2998	benign	-0.866	Destabilizing	0.971	D	0.705	prob.neutral	N	0.497238628	None	None	N
I/N	0.9538	likely_pathogenic	0.9464	pathogenic	-1.944	Destabilizing	0.999	D	0.832	deleterious	N	0.512722764	None	None	N
I/P	0.9873	likely_pathogenic	0.9844	pathogenic	-1.384	Destabilizing	0.999	D	0.841	deleterious	None	None	None	None	N
I/Q	0.9762	likely_pathogenic	0.9696	pathogenic	-1.861	Destabilizing	0.998	D	0.853	deleterious	None	None	None	None	N
I/R	0.9694	likely_pathogenic	0.9612	pathogenic	-1.437	Destabilizing	0.993	D	0.832	deleterious	None	None	None	None	N
I/S	0.9425	likely_pathogenic	0.931	pathogenic	-2.73	Highly Destabilizing	0.996	D	0.807	deleterious	D	0.52357209	None	None	N
I/T	0.8928	likely_pathogenic	0.8723	pathogenic	-2.394	Highly Destabilizing	0.922	D	0.781	deleterious	N	0.487781654	None	None	N
I/V	0.0896	likely_benign	0.0879	benign	-1.384	Destabilizing	0.002	N	0.2	neutral	N	0.39940076	None	None	N
I/W	0.9882	likely_pathogenic	0.9819	pathogenic	-1.644	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
I/Y	0.9458	likely_pathogenic	0.9277	pathogenic	-1.395	Destabilizing	0.811	D	0.797	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.