TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32007	96244;96245;96246	chr2:178544210;178544209;178544208	chr2:179408937;179408936;179408935
N2AB	30366	91321;91322;91323	chr2:178544210;178544209;178544208	chr2:179408937;179408936;179408935
N2A	29439	88540;88541;88542	chr2:178544210;178544209;178544208	chr2:179408937;179408936;179408935
N2B	22942	69049;69050;69051	chr2:178544210;178544209;178544208	chr2:179408937;179408936;179408935
Novex-1	23067	69424;69425;69426	chr2:178544210;178544209;178544208	chr2:179408937;179408936;179408935
Novex-2	23134	69625;69626;69627	chr2:178544210;178544209;178544208	chr2:179408937;179408936;179408935
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-121
• Domain position: 99
• Structural Position: 132
• Q(SASA): 0.8494
• 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
E/D	rs569522219	-0.105	0.997	N	0.595	0.144	0.281381271821	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
E/D	rs569522219	-0.105	0.997	N	0.595	0.144	0.281381271821	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/D	rs569522219	-0.105	0.997	N	0.595	0.144	0.281381271821	1000 genomes	1.99681E-04	None	None	None	None	N	None	8E-04	0	None	None	0	0	None	None	None	0	None
E/D	rs569522219	-0.105	0.997	N	0.595	0.144	0.281381271821	gnomAD-4.0.0	6.56521E-06	None	None	None	None	N	None	2.40523E-05	0	None	0	0	None	0	0	0	0	0
E/G	rs1205390409	None	0.999	N	0.622	0.473	0.608345586348	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/G	rs1205390409	None	0.999	N	0.622	0.473	0.608345586348	gnomAD-4.0.0	6.57039E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47003E-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
E/A	0.5297	ambiguous	0.4901	ambiguous	-0.195	Destabilizing	0.997	D	0.745	deleterious	N	0.495959807	None	None	N
E/C	0.9743	likely_pathogenic	0.9691	pathogenic	-0.107	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
E/D	0.1704	likely_benign	0.1812	benign	-0.252	Destabilizing	0.997	D	0.595	neutral	N	0.441973393	None	None	N
E/F	0.972	likely_pathogenic	0.9649	pathogenic	-0.115	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
E/G	0.5795	likely_pathogenic	0.5105	ambiguous	-0.356	Destabilizing	0.999	D	0.622	neutral	N	0.501479634	None	None	N
E/H	0.9047	likely_pathogenic	0.8884	pathogenic	0.308	Stabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
E/I	0.8725	likely_pathogenic	0.8429	pathogenic	0.182	Stabilizing	0.999	D	0.753	deleterious	None	None	None	None	N
E/K	0.7216	likely_pathogenic	0.661	pathogenic	0.406	Stabilizing	0.997	D	0.733	deleterious	N	0.492957257	None	None	N
E/L	0.8327	likely_pathogenic	0.8049	pathogenic	0.182	Stabilizing	0.999	D	0.707	prob.delet.	None	None	None	None	N
E/M	0.8804	likely_pathogenic	0.854	pathogenic	0.102	Stabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
E/N	0.607	likely_pathogenic	0.5915	pathogenic	0.097	Stabilizing	0.999	D	0.808	deleterious	None	None	None	None	N
E/P	0.7491	likely_pathogenic	0.7386	pathogenic	0.076	Stabilizing	0.999	D	0.785	deleterious	None	None	None	None	N
E/Q	0.4959	ambiguous	0.4478	ambiguous	0.129	Stabilizing	0.999	D	0.655	prob.neutral	N	0.482361421	None	None	N
E/R	0.8289	likely_pathogenic	0.7927	pathogenic	0.632	Stabilizing	0.999	D	0.809	deleterious	None	None	None	None	N
E/S	0.5728	likely_pathogenic	0.5305	ambiguous	-0.05	Destabilizing	0.998	D	0.758	deleterious	None	None	None	None	N
E/T	0.7449	likely_pathogenic	0.7053	pathogenic	0.087	Stabilizing	0.999	D	0.797	deleterious	None	None	None	None	N
E/V	0.7244	likely_pathogenic	0.6761	pathogenic	0.076	Stabilizing	0.999	D	0.728	deleterious	N	0.501733123	None	None	N
E/W	0.9874	likely_pathogenic	0.9838	pathogenic	-0.004	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
E/Y	0.9344	likely_pathogenic	0.9218	pathogenic	0.121	Stabilizing	1.0	D	0.773	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.