TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19719	59380;59381;59382	chr2:178592964;178592963;178592962	chr2:179457691;179457690;179457689
N2AB	18078	54457;54458;54459	chr2:178592964;178592963;178592962	chr2:179457691;179457690;179457689
N2A	17151	51676;51677;51678	chr2:178592964;178592963;178592962	chr2:179457691;179457690;179457689
N2B	10654	32185;32186;32187	chr2:178592964;178592963;178592962	chr2:179457691;179457690;179457689
Novex-1	10779	32560;32561;32562	chr2:178592964;178592963;178592962	chr2:179457691;179457690;179457689
Novex-2	10846	32761;32762;32763	chr2:178592964;178592963;178592962	chr2:179457691;179457690;179457689
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Fn3-31
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.2274
• 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
Y/D	None	None	0.995	D	0.786	0.476	0.747199188253	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	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
Y/A	0.8174	likely_pathogenic	0.7965	pathogenic	-2.601	Highly Destabilizing	0.959	D	0.723	prob.delet.	None	None	None	None	N
Y/C	0.2484	likely_benign	0.2232	benign	-1.469	Destabilizing	0.999	D	0.753	deleterious	N	0.488176955	None	None	N
Y/D	0.8886	likely_pathogenic	0.8895	pathogenic	-3.361	Highly Destabilizing	0.995	D	0.786	deleterious	D	0.523312736	None	None	N
Y/E	0.9325	likely_pathogenic	0.9223	pathogenic	-3.144	Highly Destabilizing	0.996	D	0.765	deleterious	None	None	None	None	N
Y/F	0.1094	likely_benign	0.0979	benign	-0.979	Destabilizing	0.026	N	0.277	neutral	N	0.485086665	None	None	N
Y/G	0.8402	likely_pathogenic	0.8264	pathogenic	-3.007	Highly Destabilizing	0.988	D	0.749	deleterious	None	None	None	None	N
Y/H	0.4369	ambiguous	0.4107	ambiguous	-1.903	Destabilizing	0.995	D	0.647	neutral	N	0.480761124	None	None	N
Y/I	0.6755	likely_pathogenic	0.6201	pathogenic	-1.248	Destabilizing	0.851	D	0.675	neutral	None	None	None	None	N
Y/K	0.8556	likely_pathogenic	0.8317	pathogenic	-2.141	Highly Destabilizing	0.996	D	0.767	deleterious	None	None	None	None	N
Y/L	0.664	likely_pathogenic	0.6178	pathogenic	-1.248	Destabilizing	0.034	N	0.505	neutral	None	None	None	None	N
Y/M	0.6665	likely_pathogenic	0.6078	pathogenic	-0.996	Destabilizing	0.976	D	0.741	deleterious	None	None	None	None	N
Y/N	0.6503	likely_pathogenic	0.661	pathogenic	-3.048	Highly Destabilizing	0.995	D	0.773	deleterious	N	0.500435541	None	None	N
Y/P	0.9975	likely_pathogenic	0.9972	pathogenic	-1.714	Destabilizing	0.996	D	0.791	deleterious	None	None	None	None	N
Y/Q	0.827	likely_pathogenic	0.7948	pathogenic	-2.726	Highly Destabilizing	0.996	D	0.739	prob.delet.	None	None	None	None	N
Y/R	0.8008	likely_pathogenic	0.7711	pathogenic	-2.127	Highly Destabilizing	0.996	D	0.771	deleterious	None	None	None	None	N
Y/S	0.6288	likely_pathogenic	0.6037	pathogenic	-3.294	Highly Destabilizing	0.984	D	0.737	prob.delet.	N	0.513793419	None	None	N
Y/T	0.8313	likely_pathogenic	0.804	pathogenic	-2.952	Highly Destabilizing	0.988	D	0.743	deleterious	None	None	None	None	N
Y/V	0.5697	likely_pathogenic	0.5157	ambiguous	-1.714	Destabilizing	0.851	D	0.689	prob.neutral	None	None	None	None	N
Y/W	0.5871	likely_pathogenic	0.5663	pathogenic	-0.379	Destabilizing	0.999	D	0.651	neutral	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.