TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5954	18085;18086;18087	chr2:178730673;178730672;178730671	chr2:179595400;179595399;179595398
N2AB	5637	17134;17135;17136	chr2:178730673;178730672;178730671	chr2:179595400;179595399;179595398
N2A	4710	14353;14354;14355	chr2:178730673;178730672;178730671	chr2:179595400;179595399;179595398
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: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-43
• Domain position: 36
• Structural Position: 50
• Q(SASA): 0.1574
• 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
K/T	rs1036512589	None	1.0	N	0.785	0.506	0.4897983601	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
K/T	rs1036512589	None	1.0	N	0.785	0.506	0.4897983601	gnomAD-4.0.0	1.31451E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.9404E-05	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
K/A	0.9712	likely_pathogenic	0.9478	pathogenic	-1.222	Destabilizing	0.999	D	0.697	prob.neutral	None	None	None	None	N
K/C	0.9334	likely_pathogenic	0.9027	pathogenic	-1.405	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
K/D	0.9957	likely_pathogenic	0.9921	pathogenic	-1.161	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
K/E	0.8872	likely_pathogenic	0.8102	pathogenic	-0.944	Destabilizing	0.999	D	0.597	neutral	D	0.536856363	None	None	N
K/F	0.9694	likely_pathogenic	0.9432	pathogenic	-0.853	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
K/G	0.9893	likely_pathogenic	0.9812	pathogenic	-1.667	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
K/H	0.4886	ambiguous	0.4633	ambiguous	-2.007	Highly Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
K/I	0.9031	likely_pathogenic	0.8391	pathogenic	-0.005	Destabilizing	1.0	D	0.863	deleterious	N	0.517484661	None	None	N
K/L	0.8268	likely_pathogenic	0.7326	pathogenic	-0.005	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
K/M	0.7703	likely_pathogenic	0.6719	pathogenic	-0.147	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
K/N	0.9753	likely_pathogenic	0.9584	pathogenic	-1.345	Destabilizing	1.0	D	0.738	prob.delet.	N	0.513725679	None	None	N
K/P	0.9988	likely_pathogenic	0.9977	pathogenic	-0.385	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
K/Q	0.5218	ambiguous	0.4202	ambiguous	-1.224	Destabilizing	1.0	D	0.718	prob.delet.	N	0.48178313	None	None	N
K/R	0.1128	likely_benign	0.0946	benign	-0.968	Destabilizing	0.999	D	0.607	neutral	N	0.515952998	None	None	N
K/S	0.9809	likely_pathogenic	0.9648	pathogenic	-2.01	Highly Destabilizing	0.999	D	0.632	neutral	None	None	None	None	N
K/T	0.952	likely_pathogenic	0.9142	pathogenic	-1.54	Destabilizing	1.0	D	0.785	deleterious	N	0.513472189	None	None	N
K/V	0.8936	likely_pathogenic	0.8323	pathogenic	-0.385	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
K/W	0.9496	likely_pathogenic	0.9047	pathogenic	-0.789	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
K/Y	0.9168	likely_pathogenic	0.8675	pathogenic	-0.424	Destabilizing	1.0	D	0.835	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.