TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23863	71812;71813;71814	chr2:178574545;178574544;178574543	chr2:179439272;179439271;179439270
N2AB	22222	66889;66890;66891	chr2:178574545;178574544;178574543	chr2:179439272;179439271;179439270
N2A	21295	64108;64109;64110	chr2:178574545;178574544;178574543	chr2:179439272;179439271;179439270
N2B	14798	44617;44618;44619	chr2:178574545;178574544;178574543	chr2:179439272;179439271;179439270
Novex-1	14923	44992;44993;44994	chr2:178574545;178574544;178574543	chr2:179439272;179439271;179439270
Novex-2	14990	45193;45194;45195	chr2:178574545;178574544;178574543	chr2:179439272;179439271;179439270
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-61
• Domain position: 38
• Structural Position: 40
• Q(SASA): 0.1268
• 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
V/I	rs367822322	None	None	N	0.159	0.151	0.154104182512	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
V/I	rs367822322	None	None	N	0.159	0.151	0.154104182512	gnomAD-4.0.0	6.57462E-06	None	None	None	None	N	None	2.41301E-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
V/A	0.7211	likely_pathogenic	0.588	pathogenic	-2.48	Highly Destabilizing	0.104	N	0.576	neutral	D	0.541641844	None	None	N
V/C	0.9313	likely_pathogenic	0.8755	pathogenic	-1.705	Destabilizing	0.968	D	0.777	deleterious	None	None	None	None	N
V/D	0.9979	likely_pathogenic	0.9948	pathogenic	-3.386	Highly Destabilizing	0.667	D	0.868	deleterious	D	0.553923202	None	None	N
V/E	0.992	likely_pathogenic	0.9845	pathogenic	-3.053	Highly Destabilizing	0.726	D	0.82	deleterious	None	None	None	None	N
V/F	0.8087	likely_pathogenic	0.6543	pathogenic	-1.422	Destabilizing	0.497	N	0.731	prob.delet.	D	0.553669712	None	None	N
V/G	0.9346	likely_pathogenic	0.8752	pathogenic	-3.095	Highly Destabilizing	0.667	D	0.842	deleterious	D	0.553923202	None	None	N
V/H	0.9972	likely_pathogenic	0.9935	pathogenic	-2.95	Highly Destabilizing	0.968	D	0.873	deleterious	None	None	None	None	N
V/I	0.0699	likely_benign	0.0671	benign	-0.677	Destabilizing	None	N	0.159	neutral	N	0.455878479	None	None	N
V/K	0.9935	likely_pathogenic	0.9876	pathogenic	-2.001	Highly Destabilizing	0.726	D	0.821	deleterious	None	None	None	None	N
V/L	0.3329	likely_benign	0.2536	benign	-0.677	Destabilizing	None	N	0.317	neutral	N	0.458692284	None	None	N
V/M	0.4819	ambiguous	0.3431	ambiguous	-0.88	Destabilizing	0.567	D	0.613	neutral	None	None	None	None	N
V/N	0.991	likely_pathogenic	0.9787	pathogenic	-2.734	Highly Destabilizing	0.89	D	0.877	deleterious	None	None	None	None	N
V/P	0.9803	likely_pathogenic	0.9476	pathogenic	-1.261	Destabilizing	0.89	D	0.851	deleterious	None	None	None	None	N
V/Q	0.9902	likely_pathogenic	0.9808	pathogenic	-2.348	Highly Destabilizing	0.89	D	0.867	deleterious	None	None	None	None	N
V/R	0.9878	likely_pathogenic	0.9772	pathogenic	-2.118	Highly Destabilizing	0.726	D	0.874	deleterious	None	None	None	None	N
V/S	0.9534	likely_pathogenic	0.9047	pathogenic	-3.218	Highly Destabilizing	0.726	D	0.784	deleterious	None	None	None	None	N
V/T	0.7807	likely_pathogenic	0.6535	pathogenic	-2.725	Highly Destabilizing	0.272	N	0.591	neutral	None	None	None	None	N
V/W	0.9962	likely_pathogenic	0.9882	pathogenic	-1.957	Destabilizing	0.968	D	0.853	deleterious	None	None	None	None	N
V/Y	0.9868	likely_pathogenic	0.9683	pathogenic	-1.661	Destabilizing	0.726	D	0.756	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.