TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5455	16588;16589;16590	chr2:178732698;178732697;178732696	chr2:179597425;179597424;179597423
N2AB	5138	15637;15638;15639	chr2:178732698;178732697;178732696	chr2:179597425;179597424;179597423
N2A	4211	12856;12857;12858	chr2:178732698;178732697;178732696	chr2:179597425;179597424;179597423
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-38
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.5659
• 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/E	None	None	0.026	N	0.196	0.114	0.178374595973	gnomAD-4.0.0	3.26803E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	6.1954E-05

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	0.2193	likely_benign	0.2235	benign	-0.361	Destabilizing	0.919	D	0.573	neutral	None	None	None	None	N
K/C	0.6716	likely_pathogenic	0.6586	pathogenic	-0.4	Destabilizing	0.999	D	0.703	prob.neutral	None	None	None	None	N
K/D	0.5254	ambiguous	0.5457	ambiguous	0.478	Stabilizing	0.851	D	0.557	neutral	None	None	None	None	N
K/E	0.1208	likely_benign	0.1319	benign	0.534	Stabilizing	0.026	N	0.196	neutral	N	0.46196101	None	None	N
K/F	0.595	likely_pathogenic	0.6053	pathogenic	-0.402	Destabilizing	0.996	D	0.687	prob.neutral	None	None	None	None	N
K/G	0.3651	ambiguous	0.3592	ambiguous	-0.626	Destabilizing	0.919	D	0.589	neutral	None	None	None	None	N
K/H	0.3264	likely_benign	0.3234	benign	-0.959	Destabilizing	0.988	D	0.639	neutral	None	None	None	None	N
K/I	0.2138	likely_benign	0.233	benign	0.28	Stabilizing	0.968	D	0.689	prob.neutral	N	0.499692679	None	None	N
K/L	0.2241	likely_benign	0.2307	benign	0.28	Stabilizing	0.919	D	0.607	neutral	None	None	None	None	N
K/M	0.1544	likely_benign	0.1625	benign	0.13	Stabilizing	0.999	D	0.633	neutral	None	None	None	None	N
K/N	0.3688	ambiguous	0.3881	ambiguous	0.097	Stabilizing	0.103	N	0.205	neutral	N	0.505346428	None	None	N
K/P	0.3363	likely_benign	0.3273	benign	0.096	Stabilizing	0.988	D	0.636	neutral	None	None	None	None	N
K/Q	0.1127	likely_benign	0.1126	benign	-0.026	Destabilizing	0.938	D	0.582	neutral	N	0.466502825	None	None	N
K/R	0.0855	likely_benign	0.0828	benign	-0.165	Destabilizing	0.896	D	0.528	neutral	N	0.482856357	None	None	N
K/S	0.3095	likely_benign	0.3168	benign	-0.586	Destabilizing	0.851	D	0.519	neutral	None	None	None	None	N
K/T	0.133	likely_benign	0.1355	benign	-0.343	Destabilizing	0.103	N	0.263	neutral	N	0.471890002	None	None	N
K/V	0.1973	likely_benign	0.2092	benign	0.096	Stabilizing	0.919	D	0.607	neutral	None	None	None	None	N
K/W	0.7223	likely_pathogenic	0.7144	pathogenic	-0.303	Destabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	N
K/Y	0.4925	ambiguous	0.5046	ambiguous	0.027	Stabilizing	0.996	D	0.687	prob.neutral	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.