TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10018	30277;30278;30279	chr2:178704318;178704317;178704316	chr2:179569045;179569044;179569043
N2AB	9701	29326;29327;29328	chr2:178704318;178704317;178704316	chr2:179569045;179569044;179569043
N2A	8774	26545;26546;26547	chr2:178704318;178704317;178704316	chr2:179569045;179569044;179569043
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-85
• Domain position: 30
• Structural Position: 45
• Q(SASA): 0.8769
• 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/I	None	None	0.171	None	0.366	0.304	0.457650129517	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
K/A	0.4772	ambiguous	0.5005	ambiguous	0.009	Stabilizing	0.001	N	0.184	neutral	None	None	None	None	N
K/C	0.9003	likely_pathogenic	0.9083	pathogenic	-0.381	Destabilizing	0.864	D	0.307	neutral	None	None	None	None	N
K/D	0.6895	likely_pathogenic	0.7048	pathogenic	-0.16	Destabilizing	0.038	N	0.371	neutral	None	None	None	None	N
K/E	0.2554	likely_benign	0.2503	benign	-0.15	Destabilizing	0.001	N	0.152	neutral	None	None	None	None	N
K/F	0.9085	likely_pathogenic	0.9078	pathogenic	-0.268	Destabilizing	0.356	N	0.334	neutral	None	None	None	None	N
K/G	0.6978	likely_pathogenic	0.7034	pathogenic	-0.148	Destabilizing	0.072	N	0.363	neutral	None	None	None	None	N
K/H	0.4644	ambiguous	0.4692	ambiguous	-0.246	Destabilizing	0.356	N	0.357	neutral	None	None	None	None	N
K/I	0.563	ambiguous	0.5634	ambiguous	0.347	Stabilizing	0.171	N	0.366	neutral	None	None	None	None	N
K/L	0.5539	ambiguous	0.566	pathogenic	0.347	Stabilizing	0.072	N	0.361	neutral	None	None	None	None	N
K/M	0.432	ambiguous	0.4363	ambiguous	-0.114	Destabilizing	0.628	D	0.358	neutral	None	None	None	None	N
K/N	0.5341	ambiguous	0.5388	ambiguous	0.071	Stabilizing	0.055	N	0.354	neutral	None	None	None	None	N
K/P	0.5759	likely_pathogenic	0.6114	pathogenic	0.259	Stabilizing	0.136	N	0.404	neutral	None	None	None	None	N
K/Q	0.1928	likely_benign	0.1879	benign	-0.028	Destabilizing	0.002	N	0.191	neutral	None	None	None	None	N
K/R	0.1153	likely_benign	0.1091	benign	-0.018	Destabilizing	None	N	0.231	neutral	None	None	None	None	N
K/S	0.5573	ambiguous	0.575	pathogenic	-0.297	Destabilizing	0.016	N	0.329	neutral	None	None	None	None	N
K/T	0.26	likely_benign	0.2679	benign	-0.156	Destabilizing	0.001	N	0.2	neutral	None	None	None	None	N
K/V	0.5247	ambiguous	0.546	ambiguous	0.259	Stabilizing	0.072	N	0.387	neutral	None	None	None	None	N
K/W	0.9141	likely_pathogenic	0.9031	pathogenic	-0.377	Destabilizing	0.864	D	0.335	neutral	None	None	None	None	N
K/Y	0.8201	likely_pathogenic	0.8152	pathogenic	-0.022	Destabilizing	0.356	N	0.346	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.