TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21719	65380;65381;65382	chr2:178584396;178584395;178584394	chr2:179449123;179449122;179449121
N2AB	20078	60457;60458;60459	chr2:178584396;178584395;178584394	chr2:179449123;179449122;179449121
N2A	19151	57676;57677;57678	chr2:178584396;178584395;178584394	chr2:179449123;179449122;179449121
N2B	12654	38185;38186;38187	chr2:178584396;178584395;178584394	chr2:179449123;179449122;179449121
Novex-1	12779	38560;38561;38562	chr2:178584396;178584395;178584394	chr2:179449123;179449122;179449121
Novex-2	12846	38761;38762;38763	chr2:178584396;178584395;178584394	chr2:179449123;179449122;179449121
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-45
• Domain position: 61
• Structural Position: 91
• Q(SASA): 0.1623
• 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/C	rs762352911	-1.273	1.0	N	0.837	0.492	0.587632265475	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
Y/C	rs762352911	-1.273	1.0	N	0.837	0.492	0.587632265475	gnomAD-4.0.0	6.36898E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.14407E-05	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	0.9481	likely_pathogenic	0.9436	pathogenic	-2.481	Highly Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
Y/C	0.7022	likely_pathogenic	0.6541	pathogenic	-1.358	Destabilizing	1.0	D	0.837	deleterious	N	0.514713352	None	None	N
Y/D	0.9781	likely_pathogenic	0.9767	pathogenic	-2.432	Highly Destabilizing	1.0	D	0.863	deleterious	D	0.52386526	None	None	N
Y/E	0.9851	likely_pathogenic	0.9836	pathogenic	-2.275	Highly Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
Y/F	0.1358	likely_benign	0.1212	benign	-0.87	Destabilizing	0.999	D	0.489	neutral	N	0.473557376	None	None	N
Y/G	0.9288	likely_pathogenic	0.9299	pathogenic	-2.851	Highly Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
Y/H	0.777	likely_pathogenic	0.7589	pathogenic	-1.374	Destabilizing	1.0	D	0.744	deleterious	N	0.480464273	None	None	N
Y/I	0.8399	likely_pathogenic	0.8328	pathogenic	-1.295	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
Y/K	0.9685	likely_pathogenic	0.9646	pathogenic	-1.891	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
Y/L	0.7844	likely_pathogenic	0.761	pathogenic	-1.295	Destabilizing	0.999	D	0.611	neutral	None	None	None	None	N
Y/M	0.8585	likely_pathogenic	0.8405	pathogenic	-0.955	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
Y/N	0.8571	likely_pathogenic	0.8501	pathogenic	-2.565	Highly Destabilizing	1.0	D	0.842	deleterious	D	0.52361177	None	None	N
Y/P	0.9973	likely_pathogenic	0.9974	pathogenic	-1.696	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
Y/Q	0.9623	likely_pathogenic	0.9554	pathogenic	-2.364	Highly Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
Y/R	0.9597	likely_pathogenic	0.953	pathogenic	-1.604	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
Y/S	0.897	likely_pathogenic	0.8912	pathogenic	-2.915	Highly Destabilizing	1.0	D	0.788	deleterious	D	0.523358281	None	None	N
Y/T	0.9505	likely_pathogenic	0.9473	pathogenic	-2.65	Highly Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
Y/V	0.8102	likely_pathogenic	0.7927	pathogenic	-1.696	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	N
Y/W	0.7734	likely_pathogenic	0.7501	pathogenic	-0.387	Destabilizing	1.0	D	0.724	prob.delet.	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.