TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25605	77038;77039;77040	chr2:178569319;178569318;178569317	chr2:179434046;179434045;179434044
N2AB	23964	72115;72116;72117	chr2:178569319;178569318;178569317	chr2:179434046;179434045;179434044
N2A	23037	69334;69335;69336	chr2:178569319;178569318;178569317	chr2:179434046;179434045;179434044
N2B	16540	49843;49844;49845	chr2:178569319;178569318;178569317	chr2:179434046;179434045;179434044
Novex-1	16665	50218;50219;50220	chr2:178569319;178569318;178569317	chr2:179434046;179434045;179434044
Novex-2	16732	50419;50420;50421	chr2:178569319;178569318;178569317	chr2:179434046;179434045;179434044
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-74
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.1343
• 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
P/A	rs1471696934	-2.555	0.909	D	0.773	0.664	0.51759925163	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
P/A	rs1471696934	-2.555	0.909	D	0.773	0.664	0.51759925163	gnomAD-4.0.0	1.59343E-06	None	None	None	None	N	None	0	0	None	0	2.77393E-05	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
P/A	0.4197	ambiguous	0.4375	ambiguous	-2.185	Highly Destabilizing	0.909	D	0.773	deleterious	D	0.605102788	None	None	N
P/C	0.7806	likely_pathogenic	0.7679	pathogenic	-1.896	Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
P/D	0.9991	likely_pathogenic	0.9991	pathogenic	-3.265	Highly Destabilizing	0.897	D	0.818	deleterious	None	None	None	None	N
P/E	0.9968	likely_pathogenic	0.9969	pathogenic	-3.051	Highly Destabilizing	0.933	D	0.82	deleterious	None	None	None	None	N
P/F	0.9977	likely_pathogenic	0.9979	pathogenic	-1.087	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
P/G	0.9794	likely_pathogenic	0.9804	pathogenic	-2.675	Highly Destabilizing	0.97	D	0.849	deleterious	None	None	None	None	N
P/H	0.9961	likely_pathogenic	0.9962	pathogenic	-2.421	Highly Destabilizing	1.0	D	0.862	deleterious	D	0.661427717	None	None	N
P/I	0.7121	likely_pathogenic	0.7361	pathogenic	-0.801	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
P/K	0.9988	likely_pathogenic	0.9988	pathogenic	-1.82	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
P/L	0.7708	likely_pathogenic	0.7964	pathogenic	-0.801	Destabilizing	0.882	D	0.774	deleterious	D	0.661024108	None	None	N
P/M	0.9466	likely_pathogenic	0.9496	pathogenic	-1.079	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
P/N	0.9966	likely_pathogenic	0.9965	pathogenic	-2.211	Highly Destabilizing	0.965	D	0.861	deleterious	None	None	None	None	N
P/Q	0.9924	likely_pathogenic	0.9927	pathogenic	-2.036	Highly Destabilizing	0.994	D	0.797	deleterious	None	None	None	None	N
P/R	0.9948	likely_pathogenic	0.9951	pathogenic	-1.645	Destabilizing	0.997	D	0.857	deleterious	D	0.661225913	None	None	N
P/S	0.9245	likely_pathogenic	0.9267	pathogenic	-2.694	Highly Destabilizing	0.679	D	0.709	prob.delet.	D	0.644772583	None	None	N
P/T	0.7398	likely_pathogenic	0.7448	pathogenic	-2.363	Highly Destabilizing	0.938	D	0.815	deleterious	D	0.661225913	None	None	N
P/V	0.3691	ambiguous	0.3946	ambiguous	-1.24	Destabilizing	0.992	D	0.847	deleterious	None	None	None	None	N
P/W	0.9997	likely_pathogenic	0.9997	pathogenic	-1.685	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
P/Y	0.9992	likely_pathogenic	0.9992	pathogenic	-1.387	Destabilizing	1.0	D	0.897	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.