TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10005	30238;30239;30240	chr2:178704357;178704356;178704355	chr2:179569084;179569083;179569082
N2AB	9688	29287;29288;29289	chr2:178704357;178704356;178704355	chr2:179569084;179569083;179569082
N2A	8761	26506;26507;26508	chr2:178704357;178704356;178704355	chr2:179569084;179569083;179569082
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: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-85
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.4961
• 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
T/I	rs2075505818	None	0.984	None	0.623	0.278	0.331876078066	gnomAD-4.0.0	1.59101E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85791E-06	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
T/A	0.1639	likely_benign	0.1576	benign	-0.654	Destabilizing	0.64	D	0.433	neutral	None	None	None	None	N
T/C	0.7745	likely_pathogenic	0.8174	pathogenic	-0.37	Destabilizing	0.999	D	0.631	neutral	None	None	None	None	N
T/D	0.6512	likely_pathogenic	0.6274	pathogenic	-0.046	Destabilizing	0.919	D	0.534	neutral	None	None	None	None	N
T/E	0.5209	ambiguous	0.4842	ambiguous	-0.085	Destabilizing	0.919	D	0.521	neutral	None	None	None	None	N
T/F	0.4874	ambiguous	0.5127	ambiguous	-0.904	Destabilizing	0.996	D	0.712	prob.delet.	None	None	None	None	N
T/G	0.5627	ambiguous	0.5748	pathogenic	-0.861	Destabilizing	0.851	D	0.557	neutral	None	None	None	None	N
T/H	0.4701	ambiguous	0.483	ambiguous	-1.165	Destabilizing	0.999	D	0.705	prob.neutral	None	None	None	None	N
T/I	0.2611	likely_benign	0.2671	benign	-0.209	Destabilizing	0.984	D	0.623	neutral	None	None	None	None	N
T/K	0.3473	ambiguous	0.3347	benign	-0.6	Destabilizing	0.919	D	0.533	neutral	None	None	None	None	N
T/L	0.1978	likely_benign	0.2114	benign	-0.209	Destabilizing	0.919	D	0.537	neutral	None	None	None	None	N
T/M	0.1364	likely_benign	0.1348	benign	0.103	Stabilizing	0.999	D	0.622	neutral	None	None	None	None	N
T/N	0.2212	likely_benign	0.2096	benign	-0.438	Destabilizing	0.968	D	0.487	neutral	None	None	None	None	N
T/P	0.2577	likely_benign	0.2797	benign	-0.326	Destabilizing	0.026	N	0.292	neutral	None	None	None	None	N
T/Q	0.3914	ambiguous	0.3828	ambiguous	-0.666	Destabilizing	0.988	D	0.638	neutral	None	None	None	None	N
T/R	0.3065	likely_benign	0.2957	benign	-0.314	Destabilizing	0.976	D	0.631	neutral	None	None	None	None	N
T/S	0.2086	likely_benign	0.2036	benign	-0.705	Destabilizing	0.103	N	0.162	neutral	None	None	None	None	N
T/V	0.2317	likely_benign	0.2413	benign	-0.326	Destabilizing	0.919	D	0.455	neutral	None	None	None	None	N
T/W	0.8344	likely_pathogenic	0.8552	pathogenic	-0.839	Destabilizing	0.999	D	0.727	prob.delet.	None	None	None	None	N
T/Y	0.5349	ambiguous	0.5667	pathogenic	-0.599	Destabilizing	0.996	D	0.717	prob.delet.	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.