TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6914	20965;20966;20967	chr2:178725464;178725463;178725462	chr2:179590191;179590190;179590189
N2AB	6597	20014;20015;20016	chr2:178725464;178725463;178725462	chr2:179590191;179590190;179590189
N2A	5670	17233;17234;17235	chr2:178725464;178725463;178725462	chr2:179590191;179590190;179590189
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: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-53
• Domain position: 61
• Structural Position: 140
• Q(SASA): 0.1775
• 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
F/L	rs397517495	-1.394	None	N	0.317	0.129	0.311079019809	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
F/L	rs397517495	-1.394	None	N	0.317	0.129	0.311079019809	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
F/L	rs397517495	-1.394	None	N	0.317	0.129	0.311079019809	gnomAD-4.0.0	1.36396E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.8653E-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
F/A	0.8248	likely_pathogenic	0.847	pathogenic	-3.26	Highly Destabilizing	0.061	N	0.57	neutral	None	None	None	None	N
F/C	0.5592	ambiguous	0.5754	pathogenic	-2.433	Highly Destabilizing	0.921	D	0.769	deleterious	N	0.505064486	None	None	N
F/D	0.9754	likely_pathogenic	0.9828	pathogenic	-3.668	Highly Destabilizing	0.418	N	0.737	prob.delet.	None	None	None	None	N
F/E	0.974	likely_pathogenic	0.9799	pathogenic	-3.477	Highly Destabilizing	0.418	N	0.727	prob.delet.	None	None	None	None	N
F/G	0.9486	likely_pathogenic	0.9582	pathogenic	-3.71	Highly Destabilizing	0.228	N	0.72	prob.delet.	None	None	None	None	N
F/H	0.917	likely_pathogenic	0.9283	pathogenic	-2.136	Highly Destabilizing	0.94	D	0.713	prob.delet.	None	None	None	None	N
F/I	0.1099	likely_benign	0.1152	benign	-1.786	Destabilizing	0.001	N	0.294	neutral	N	0.388660904	None	None	N
F/K	0.9781	likely_pathogenic	0.9846	pathogenic	-2.496	Highly Destabilizing	0.418	N	0.724	prob.delet.	None	None	None	None	N
F/L	0.6126	likely_pathogenic	0.5792	pathogenic	-1.786	Destabilizing	None	N	0.317	neutral	N	0.452227672	None	None	N
F/M	0.3872	ambiguous	0.394	ambiguous	-1.578	Destabilizing	0.716	D	0.622	neutral	None	None	None	None	N
F/N	0.9338	likely_pathogenic	0.9509	pathogenic	-2.939	Highly Destabilizing	0.418	N	0.751	deleterious	None	None	None	None	N
F/P	0.9903	likely_pathogenic	0.9922	pathogenic	-2.29	Highly Destabilizing	0.593	D	0.771	deleterious	None	None	None	None	N
F/Q	0.9602	likely_pathogenic	0.9674	pathogenic	-2.947	Highly Destabilizing	0.836	D	0.791	deleterious	None	None	None	None	N
F/R	0.9575	likely_pathogenic	0.9664	pathogenic	-1.83	Destabilizing	0.593	D	0.779	deleterious	None	None	None	None	N
F/S	0.8703	likely_pathogenic	0.8945	pathogenic	-3.621	Highly Destabilizing	0.009	N	0.513	neutral	N	0.504810996	None	None	N
F/T	0.8181	likely_pathogenic	0.8409	pathogenic	-3.315	Highly Destabilizing	0.129	N	0.639	neutral	None	None	None	None	N
F/V	0.1942	likely_benign	0.2068	benign	-2.29	Highly Destabilizing	0.001	N	0.451	neutral	N	0.455171977	None	None	N
F/W	0.6214	likely_pathogenic	0.6372	pathogenic	-0.76	Destabilizing	0.983	D	0.583	neutral	None	None	None	None	N
F/Y	0.3758	ambiguous	0.3874	ambiguous	-1.193	Destabilizing	0.523	D	0.521	neutral	N	0.505064486	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.