TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17760	53503;53504;53505	chr2:178607410;178607409;178607408	chr2:179472137;179472136;179472135
N2AB	16119	48580;48581;48582	chr2:178607410;178607409;178607408	chr2:179472137;179472136;179472135
N2A	15192	45799;45800;45801	chr2:178607410;178607409;178607408	chr2:179472137;179472136;179472135
N2B	8695	26308;26309;26310	chr2:178607410;178607409;178607408	chr2:179472137;179472136;179472135
Novex-1	8820	26683;26684;26685	chr2:178607410;178607409;178607408	chr2:179472137;179472136;179472135
Novex-2	8887	26884;26885;26886	chr2:178607410;178607409;178607408	chr2:179472137;179472136;179472135
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: Ig-113
• Domain position: 84
• Structural Position: 175
• Q(SASA): 0.4324
• 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/G	rs2055156080	None	0.994	N	0.604	0.535	0.549078225428	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
E/Q	None	None	0.989	N	0.516	0.355	0.273503213844	gnomAD-4.0.0	1.5927E-06	None	None	None	None	N	None	5.66829E-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
E/A	0.4617	ambiguous	0.5033	ambiguous	-0.863	Destabilizing	0.994	D	0.547	neutral	N	0.46746927	None	None	N
E/C	0.9598	likely_pathogenic	0.9677	pathogenic	-0.621	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
E/D	0.1876	likely_benign	0.2164	benign	-1.334	Destabilizing	0.217	N	0.333	neutral	N	0.41221342	None	None	N
E/F	0.9326	likely_pathogenic	0.9426	pathogenic	-0.09	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
E/G	0.6995	likely_pathogenic	0.7313	pathogenic	-1.286	Destabilizing	0.994	D	0.604	neutral	N	0.482766797	None	None	N
E/H	0.8104	likely_pathogenic	0.8355	pathogenic	-0.459	Destabilizing	1.0	D	0.532	neutral	None	None	None	None	N
E/I	0.6728	likely_pathogenic	0.7045	pathogenic	0.314	Stabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
E/K	0.6123	likely_pathogenic	0.6274	pathogenic	-1.104	Destabilizing	0.978	D	0.483	neutral	N	0.392720796	None	None	N
E/L	0.7749	likely_pathogenic	0.8017	pathogenic	0.314	Stabilizing	0.999	D	0.685	prob.neutral	None	None	None	None	N
E/M	0.7853	likely_pathogenic	0.7926	pathogenic	0.814	Stabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
E/N	0.5078	ambiguous	0.5585	ambiguous	-1.555	Destabilizing	0.998	D	0.549	neutral	None	None	None	None	N
E/P	0.9923	likely_pathogenic	0.9926	pathogenic	-0.057	Destabilizing	1.0	D	0.651	neutral	None	None	None	None	N
E/Q	0.4113	ambiguous	0.4278	ambiguous	-1.349	Destabilizing	0.989	D	0.516	neutral	N	0.432297904	None	None	N
E/R	0.7199	likely_pathogenic	0.7442	pathogenic	-0.771	Destabilizing	0.46	N	0.289	neutral	None	None	None	None	N
E/S	0.5045	ambiguous	0.5431	ambiguous	-1.968	Destabilizing	0.992	D	0.507	neutral	None	None	None	None	N
E/T	0.4886	ambiguous	0.5259	ambiguous	-1.616	Destabilizing	0.999	D	0.604	neutral	None	None	None	None	N
E/V	0.4605	ambiguous	0.4831	ambiguous	-0.057	Destabilizing	0.998	D	0.702	prob.neutral	N	0.443901764	None	None	N
E/W	0.9767	likely_pathogenic	0.9795	pathogenic	0.111	Stabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
E/Y	0.8867	likely_pathogenic	0.9061	pathogenic	0.131	Stabilizing	1.0	D	0.719	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.