TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32724	98395;98396;98397	chr2:178539895;178539894;178539893	chr2:179404622;179404621;179404620
N2AB	31083	93472;93473;93474	chr2:178539895;178539894;178539893	chr2:179404622;179404621;179404620
N2A	30156	90691;90692;90693	chr2:178539895;178539894;178539893	chr2:179404622;179404621;179404620
N2B	23659	71200;71201;71202	chr2:178539895;178539894;178539893	chr2:179404622;179404621;179404620
Novex-1	23784	71575;71576;71577	chr2:178539895;178539894;178539893	chr2:179404622;179404621;179404620
Novex-2	23851	71776;71777;71778	chr2:178539895;178539894;178539893	chr2:179404622;179404621;179404620
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-155
• Domain position: 17
• Structural Position: 30
• Q(SASA): 0.2332
• 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/P	None	None	0.999	D	0.85	0.75	0.904252142976	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-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
L/A	0.9409	likely_pathogenic	0.9287	pathogenic	-1.588	Destabilizing	0.983	D	0.748	deleterious	None	None	None	None	N
L/C	0.9019	likely_pathogenic	0.8763	pathogenic	-1.286	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
L/D	0.9989	likely_pathogenic	0.9983	pathogenic	-2.537	Highly Destabilizing	0.999	D	0.855	deleterious	None	None	None	None	N
L/E	0.9935	likely_pathogenic	0.9907	pathogenic	-2.281	Highly Destabilizing	0.999	D	0.843	deleterious	None	None	None	None	N
L/F	0.4767	ambiguous	0.3951	ambiguous	-1.134	Destabilizing	0.993	D	0.777	deleterious	D	0.534424981	None	None	N
L/G	0.9901	likely_pathogenic	0.9881	pathogenic	-2.036	Highly Destabilizing	0.999	D	0.855	deleterious	None	None	None	None	N
L/H	0.9797	likely_pathogenic	0.9693	pathogenic	-2.203	Highly Destabilizing	1.0	D	0.831	deleterious	D	0.598271803	None	None	N
L/I	0.1276	likely_benign	0.1057	benign	-0.248	Destabilizing	0.235	N	0.412	neutral	N	0.492722129	None	None	N
L/K	0.9868	likely_pathogenic	0.9815	pathogenic	-1.424	Destabilizing	0.998	D	0.841	deleterious	None	None	None	None	N
L/M	0.2357	likely_benign	0.1772	benign	-0.633	Destabilizing	0.995	D	0.739	prob.delet.	None	None	None	None	N
L/N	0.992	likely_pathogenic	0.988	pathogenic	-2.088	Highly Destabilizing	0.999	D	0.852	deleterious	None	None	None	None	N
L/P	0.9943	likely_pathogenic	0.9923	pathogenic	-0.687	Destabilizing	0.999	D	0.85	deleterious	D	0.598271803	None	None	N
L/Q	0.977	likely_pathogenic	0.9655	pathogenic	-1.684	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
L/R	0.9812	likely_pathogenic	0.9743	pathogenic	-1.842	Destabilizing	0.999	D	0.835	deleterious	D	0.598271803	None	None	N
L/S	0.9918	likely_pathogenic	0.9879	pathogenic	-2.39	Highly Destabilizing	0.998	D	0.844	deleterious	None	None	None	None	N
L/T	0.9697	likely_pathogenic	0.9586	pathogenic	-1.991	Destabilizing	0.995	D	0.789	deleterious	None	None	None	None	N
L/V	0.2558	likely_benign	0.2161	benign	-0.687	Destabilizing	0.898	D	0.676	prob.neutral	D	0.532953173	None	None	N
L/W	0.9315	likely_pathogenic	0.896	pathogenic	-1.478	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
L/Y	0.9331	likely_pathogenic	0.9008	pathogenic	-1.241	Destabilizing	0.999	D	0.787	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.