TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32515	97768;97769;97770	chr2:178541534;178541533;178541532	chr2:179406261;179406260;179406259
N2AB	30874	92845;92846;92847	chr2:178541534;178541533;178541532	chr2:179406261;179406260;179406259
N2A	29947	90064;90065;90066	chr2:178541534;178541533;178541532	chr2:179406261;179406260;179406259
N2B	23450	70573;70574;70575	chr2:178541534;178541533;178541532	chr2:179406261;179406260;179406259
Novex-1	23575	70948;70949;70950	chr2:178541534;178541533;178541532	chr2:179406261;179406260;179406259
Novex-2	23642	71149;71150;71151	chr2:178541534;178541533;178541532	chr2:179406261;179406260;179406259
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Fn3-125
• Domain position: 17
• Structural Position: 19
• Q(SASA): 0.1069
• 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
G/A	None	None	1.0	N	0.615	0.407	0.247872288689	gnomAD-4.0.0	1.59417E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86305E-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
G/A	0.1671	likely_benign	0.1307	benign	-0.47	Destabilizing	1.0	D	0.615	neutral	N	0.418354667	None	None	N
G/C	0.3053	likely_benign	0.2256	benign	-1.792	Destabilizing	1.0	D	0.792	deleterious	N	0.47442138	None	None	N
G/D	0.8006	likely_pathogenic	0.7222	pathogenic	-2.711	Highly Destabilizing	1.0	D	0.861	deleterious	N	0.512342263	None	None	N
G/E	0.7246	likely_pathogenic	0.6513	pathogenic	-2.698	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
G/F	0.8525	likely_pathogenic	0.7874	pathogenic	-0.978	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
G/H	0.7414	likely_pathogenic	0.6487	pathogenic	-0.744	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
G/I	0.715	likely_pathogenic	0.5932	pathogenic	-0.167	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
G/K	0.8827	likely_pathogenic	0.8325	pathogenic	-1.089	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
G/L	0.8299	likely_pathogenic	0.7338	pathogenic	-0.167	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
G/M	0.7648	likely_pathogenic	0.672	pathogenic	-0.557	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
G/N	0.7022	likely_pathogenic	0.583	pathogenic	-1.379	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
G/P	0.9968	likely_pathogenic	0.9948	pathogenic	-0.236	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
G/Q	0.7269	likely_pathogenic	0.6451	pathogenic	-1.591	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
G/R	0.7149	likely_pathogenic	0.6473	pathogenic	-0.827	Destabilizing	1.0	D	0.883	deleterious	N	0.479133767	None	None	N
G/S	0.1233	likely_benign	0.0928	benign	-1.459	Destabilizing	1.0	D	0.717	prob.delet.	N	0.357644564	None	None	N
G/T	0.3337	likely_benign	0.2609	benign	-1.389	Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
G/V	0.5711	likely_pathogenic	0.4458	ambiguous	-0.236	Destabilizing	1.0	D	0.875	deleterious	N	0.479653842	None	None	N
G/W	0.7601	likely_pathogenic	0.6952	pathogenic	-1.377	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
G/Y	0.7661	likely_pathogenic	0.6775	pathogenic	-0.881	Destabilizing	1.0	D	0.848	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.