TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8555	25888;25889;25890	chr2:178715751;178715750;178715749	chr2:179580478;179580477;179580476
N2AB	8238	24937;24938;24939	chr2:178715751;178715750;178715749	chr2:179580478;179580477;179580476
N2A	7311	22156;22157;22158	chr2:178715751;178715750;178715749	chr2:179580478;179580477;179580476
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Ig-71
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.1237
• 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
L/Q	None	None	1.0	D	0.863	0.354	0.721541066513	gnomAD-4.0.0	6.96823E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.11472E-07	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
L/A	0.7366	likely_pathogenic	0.7394	pathogenic	-2.31	Highly Destabilizing	0.999	D	0.717	prob.delet.	None	None	None	None	N
L/C	0.9338	likely_pathogenic	0.931	pathogenic	-1.59	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
L/D	0.9946	likely_pathogenic	0.9939	pathogenic	-2.127	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
L/E	0.9646	likely_pathogenic	0.9611	pathogenic	-1.958	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
L/F	0.6882	likely_pathogenic	0.6872	pathogenic	-1.381	Destabilizing	0.999	D	0.745	deleterious	None	None	None	None	N
L/G	0.9485	likely_pathogenic	0.9491	pathogenic	-2.815	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
L/H	0.9598	likely_pathogenic	0.955	pathogenic	-2.217	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
L/I	0.1947	likely_benign	0.2028	benign	-0.884	Destabilizing	0.963	D	0.552	neutral	N	0.477193865	None	None	N
L/K	0.9663	likely_pathogenic	0.963	pathogenic	-1.576	Destabilizing	0.992	D	0.846	deleterious	None	None	None	None	N
L/M	0.2311	likely_benign	0.239	benign	-0.814	Destabilizing	0.998	D	0.742	deleterious	None	None	None	None	N
L/N	0.9649	likely_pathogenic	0.9612	pathogenic	-1.693	Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
L/P	0.5705	likely_pathogenic	0.5658	pathogenic	-1.336	Destabilizing	1.0	D	0.872	deleterious	N	0.472023288	None	None	N
L/Q	0.8822	likely_pathogenic	0.8732	pathogenic	-1.64	Destabilizing	1.0	D	0.863	deleterious	D	0.528912964	None	None	N
L/R	0.9399	likely_pathogenic	0.9344	pathogenic	-1.271	Destabilizing	0.999	D	0.861	deleterious	D	0.528912964	None	None	N
L/S	0.9426	likely_pathogenic	0.9389	pathogenic	-2.448	Highly Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
L/T	0.7321	likely_pathogenic	0.7296	pathogenic	-2.137	Highly Destabilizing	0.999	D	0.789	deleterious	None	None	None	None	N
L/V	0.2148	likely_benign	0.2194	benign	-1.336	Destabilizing	0.972	D	0.529	neutral	N	0.471282063	None	None	N
L/W	0.9049	likely_pathogenic	0.899	pathogenic	-1.674	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
L/Y	0.9636	likely_pathogenic	0.9615	pathogenic	-1.407	Destabilizing	0.995	D	0.837	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.