TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31887	95884;95885;95886	chr2:178545451;178545450;178545449	chr2:179410178;179410177;179410176
N2AB	30246	90961;90962;90963	chr2:178545451;178545450;178545449	chr2:179410178;179410177;179410176
N2A	29319	88180;88181;88182	chr2:178545451;178545450;178545449	chr2:179410178;179410177;179410176
N2B	22822	68689;68690;68691	chr2:178545451;178545450;178545449	chr2:179410178;179410177;179410176
Novex-1	22947	69064;69065;69066	chr2:178545451;178545450;178545449	chr2:179410178;179410177;179410176
Novex-2	23014	69265;69266;69267	chr2:178545451;178545450;178545449	chr2:179410178;179410177;179410176
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-120
• Domain position: 81
• Structural Position: 112
• Q(SASA): 0.1525
• 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
N/I	None	None	1.0	D	0.791	0.671	0.854727020446	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
N/A	0.9969	likely_pathogenic	0.9958	pathogenic	-0.041	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
N/C	0.9591	likely_pathogenic	0.9452	pathogenic	-0.145	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
N/D	0.9906	likely_pathogenic	0.9877	pathogenic	-2.168	Highly Destabilizing	0.999	D	0.644	neutral	D	0.564494769	None	None	N
N/E	0.9988	likely_pathogenic	0.9986	pathogenic	-2.051	Highly Destabilizing	0.999	D	0.739	prob.delet.	None	None	None	None	N
N/F	0.9993	likely_pathogenic	0.9991	pathogenic	-0.238	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
N/G	0.9897	likely_pathogenic	0.988	pathogenic	-0.318	Destabilizing	0.999	D	0.613	neutral	None	None	None	None	N
N/H	0.9825	likely_pathogenic	0.9765	pathogenic	-0.271	Destabilizing	1.0	D	0.788	deleterious	D	0.566269196	None	None	N
N/I	0.9957	likely_pathogenic	0.994	pathogenic	0.633	Stabilizing	1.0	D	0.791	deleterious	D	0.566522685	None	None	N
N/K	0.9989	likely_pathogenic	0.9986	pathogenic	0.102	Stabilizing	1.0	D	0.767	deleterious	D	0.565255238	None	None	N
N/L	0.9798	likely_pathogenic	0.9774	pathogenic	0.633	Stabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
N/M	0.9943	likely_pathogenic	0.9921	pathogenic	0.899	Stabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
N/P	0.9981	likely_pathogenic	0.9981	pathogenic	0.438	Stabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
N/Q	0.9988	likely_pathogenic	0.9984	pathogenic	-0.951	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
N/R	0.9976	likely_pathogenic	0.9974	pathogenic	0.177	Stabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
N/S	0.8511	likely_pathogenic	0.8051	pathogenic	-0.602	Destabilizing	0.999	D	0.633	neutral	D	0.523980618	None	None	N
N/T	0.9655	likely_pathogenic	0.9506	pathogenic	-0.346	Destabilizing	0.999	D	0.731	prob.delet.	D	0.528852009	None	None	N
N/V	0.9937	likely_pathogenic	0.9914	pathogenic	0.438	Stabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
N/W	0.9998	likely_pathogenic	0.9998	pathogenic	-0.328	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
N/Y	0.9948	likely_pathogenic	0.994	pathogenic	0.195	Stabilizing	1.0	D	0.804	deleterious	D	0.566269196	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.