TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32419	97480;97481;97482	chr2:178542501;178542500;178542499	chr2:179407228;179407227;179407226
N2AB	30778	92557;92558;92559	chr2:178542501;178542500;178542499	chr2:179407228;179407227;179407226
N2A	29851	89776;89777;89778	chr2:178542501;178542500;178542499	chr2:179407228;179407227;179407226
N2B	23354	70285;70286;70287	chr2:178542501;178542500;178542499	chr2:179407228;179407227;179407226
Novex-1	23479	70660;70661;70662	chr2:178542501;178542500;178542499	chr2:179407228;179407227;179407226
Novex-2	23546	70861;70862;70863	chr2:178542501;178542500;178542499	chr2:179407228;179407227;179407226
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: Fn3-124
• Domain position: 21
• Structural Position: 22
• Q(SASA): 0.0521
• 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	rs746131466	-1.272	0.011	N	0.163	0.057	0.312001716656	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.79E-05	0
I/V	rs746131466	-1.272	0.011	N	0.163	0.057	0.312001716656	gnomAD-4.0.0	3.18845E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.73181E-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	0.6879	likely_pathogenic	0.6342	pathogenic	-2.275	Highly Destabilizing	0.702	D	0.735	prob.delet.	None	None	None	None	N
I/C	0.7632	likely_pathogenic	0.7363	pathogenic	-1.137	Destabilizing	0.076	N	0.647	neutral	None	None	None	None	N
I/D	0.998	likely_pathogenic	0.9975	pathogenic	-2.687	Highly Destabilizing	0.996	D	0.939	deleterious	None	None	None	None	N
I/E	0.9958	likely_pathogenic	0.995	pathogenic	-2.36	Highly Destabilizing	0.988	D	0.935	deleterious	None	None	None	None	N
I/F	0.4595	ambiguous	0.3967	ambiguous	-1.291	Destabilizing	0.984	D	0.729	prob.delet.	N	0.474103588	None	None	N
I/G	0.9677	likely_pathogenic	0.9549	pathogenic	-2.86	Highly Destabilizing	0.988	D	0.902	deleterious	None	None	None	None	N
I/H	0.9927	likely_pathogenic	0.991	pathogenic	-2.811	Highly Destabilizing	0.999	D	0.927	deleterious	None	None	None	None	N
I/K	0.9945	likely_pathogenic	0.994	pathogenic	-1.295	Destabilizing	0.988	D	0.936	deleterious	None	None	None	None	N
I/L	0.132	likely_benign	0.1191	benign	-0.495	Destabilizing	0.437	N	0.387	neutral	N	0.347218848	None	None	N
I/M	0.1688	likely_benign	0.1529	benign	-0.788	Destabilizing	0.984	D	0.699	prob.neutral	N	0.455175589	None	None	N
I/N	0.9755	likely_pathogenic	0.9721	pathogenic	-2.041	Highly Destabilizing	0.995	D	0.934	deleterious	N	0.499221686	None	None	N
I/P	0.9961	likely_pathogenic	0.9953	pathogenic	-1.083	Destabilizing	0.996	D	0.935	deleterious	None	None	None	None	N
I/Q	0.9899	likely_pathogenic	0.9887	pathogenic	-1.589	Destabilizing	0.996	D	0.937	deleterious	None	None	None	None	N
I/R	0.9897	likely_pathogenic	0.9879	pathogenic	-1.738	Destabilizing	0.996	D	0.934	deleterious	None	None	None	None	N
I/S	0.9225	likely_pathogenic	0.9058	pathogenic	-2.447	Highly Destabilizing	0.984	D	0.871	deleterious	N	0.48786538	None	None	N
I/T	0.848	likely_pathogenic	0.8202	pathogenic	-1.952	Destabilizing	0.896	D	0.766	deleterious	N	0.487611891	None	None	N
I/V	0.0779	likely_benign	0.0707	benign	-1.083	Destabilizing	0.011	N	0.163	neutral	N	0.434923551	None	None	N
I/W	0.9922	likely_pathogenic	0.9892	pathogenic	-1.55	Destabilizing	0.999	D	0.905	deleterious	None	None	None	None	N
I/Y	0.9568	likely_pathogenic	0.9461	pathogenic	-1.424	Destabilizing	0.996	D	0.841	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.