TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29768	89527;89528;89529	chr2:178553703;178553702;178553701	chr2:179418430;179418429;179418428
N2AB	28127	84604;84605;84606	chr2:178553703;178553702;178553701	chr2:179418430;179418429;179418428
N2A	27200	81823;81824;81825	chr2:178553703;178553702;178553701	chr2:179418430;179418429;179418428
N2B	20703	62332;62333;62334	chr2:178553703;178553702;178553701	chr2:179418430;179418429;179418428
Novex-1	20828	62707;62708;62709	chr2:178553703;178553702;178553701	chr2:179418430;179418429;179418428
Novex-2	20895	62908;62909;62910	chr2:178553703;178553702;178553701	chr2:179418430;179418429;179418428
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGG
• RefSeq wild type template codon: CCC
• Domain: Fn3-105
• Domain position: 35
• Structural Position: 37
• Q(SASA): 0.0983
• 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/R	None	None	0.549	N	0.759	0.249	0.593372671839	gnomAD-4.0.0	2.05261E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69838E-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	0.2732	likely_benign	0.2654	benign	-0.628	Destabilizing	0.201	N	0.375	neutral	N	0.473756003	None	None	N
G/C	0.4639	ambiguous	0.4467	ambiguous	-0.888	Destabilizing	0.992	D	0.759	deleterious	None	None	None	None	N
G/D	0.7329	likely_pathogenic	0.7159	pathogenic	-0.918	Destabilizing	0.447	N	0.711	prob.delet.	None	None	None	None	N
G/E	0.7592	likely_pathogenic	0.7876	pathogenic	-0.944	Destabilizing	0.004	N	0.579	neutral	N	0.521602039	None	None	N
G/F	0.9331	likely_pathogenic	0.9272	pathogenic	-0.846	Destabilizing	0.92	D	0.789	deleterious	None	None	None	None	N
G/H	0.7512	likely_pathogenic	0.7428	pathogenic	-1.244	Destabilizing	0.005	N	0.573	neutral	None	None	None	None	N
G/I	0.9113	likely_pathogenic	0.902	pathogenic	-0.169	Destabilizing	0.92	D	0.798	deleterious	None	None	None	None	N
G/K	0.8554	likely_pathogenic	0.8725	pathogenic	-1.02	Destabilizing	0.447	N	0.744	deleterious	None	None	None	None	N
G/L	0.8995	likely_pathogenic	0.8882	pathogenic	-0.169	Destabilizing	0.617	D	0.773	deleterious	None	None	None	None	N
G/M	0.8885	likely_pathogenic	0.8813	pathogenic	-0.276	Destabilizing	0.992	D	0.763	deleterious	None	None	None	None	N
G/N	0.6749	likely_pathogenic	0.6402	pathogenic	-0.776	Destabilizing	0.617	D	0.577	neutral	None	None	None	None	N
G/P	0.9984	likely_pathogenic	0.9979	pathogenic	-0.28	Destabilizing	0.92	D	0.781	deleterious	None	None	None	None	N
G/Q	0.7431	likely_pathogenic	0.7495	pathogenic	-0.901	Destabilizing	0.447	N	0.769	deleterious	None	None	None	None	N
G/R	0.7318	likely_pathogenic	0.7351	pathogenic	-0.837	Destabilizing	0.549	D	0.759	deleterious	N	0.478173322	None	None	N
G/S	0.1706	likely_benign	0.1612	benign	-1.098	Destabilizing	0.003	N	0.169	neutral	None	None	None	None	N
G/T	0.5271	ambiguous	0.5266	ambiguous	-1.036	Destabilizing	0.447	N	0.744	deleterious	None	None	None	None	N
G/V	0.8228	likely_pathogenic	0.8041	pathogenic	-0.28	Destabilizing	0.549	D	0.783	deleterious	D	0.527259074	None	None	N
G/W	0.8504	likely_pathogenic	0.8437	pathogenic	-1.243	Destabilizing	0.99	D	0.741	deleterious	N	0.516752143	None	None	N
G/Y	0.8338	likely_pathogenic	0.8135	pathogenic	-0.785	Destabilizing	0.85	D	0.805	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.