TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26302	79129;79130;79131	chr2:178567228;178567227;178567226	chr2:179431955;179431954;179431953
N2AB	24661	74206;74207;74208	chr2:178567228;178567227;178567226	chr2:179431955;179431954;179431953
N2A	23734	71425;71426;71427	chr2:178567228;178567227;178567226	chr2:179431955;179431954;179431953
N2B	17237	51934;51935;51936	chr2:178567228;178567227;178567226	chr2:179431955;179431954;179431953
Novex-1	17362	52309;52310;52311	chr2:178567228;178567227;178567226	chr2:179431955;179431954;179431953
Novex-2	17429	52510;52511;52512	chr2:178567228;178567227;178567226	chr2:179431955;179431954;179431953
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: Fn3-79
• Domain position: 17
• Structural Position: 18
• Q(SASA): 0.4962
• 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	rs534003014	-0.504	0.011	N	0.131	0.033	0.130388298395	gnomAD-2.1.1	6.16E-05	None	None	None	None	N	None	4.14E-05	0	None	0	0	None	0	None	0	1.26687E-04	0
E/D	rs534003014	-0.504	0.011	N	0.131	0.033	0.130388298395	gnomAD-3.1.2	8.55E-05	None	None	None	None	N	None	7.24E-05	6.55E-05	0	0	0	None	0	0	1.32376E-04	0	0
E/D	rs534003014	-0.504	0.011	N	0.131	0.033	0.130388298395	gnomAD-4.0.0	1.91421E-04	None	None	None	None	N	None	1.87271E-04	5.03761E-05	None	0	0	None	0	0	2.41268E-04	0	1.12504E-04

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	0.537	ambiguous	0.5501	ambiguous	-0.686	Destabilizing	0.892	D	0.569	neutral	N	0.515286568	None	None	N
E/C	0.9638	likely_pathogenic	0.9639	pathogenic	-0.068	Destabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	N
E/D	0.1482	likely_benign	0.1862	benign	-0.806	Destabilizing	0.011	N	0.131	neutral	N	0.470012851	None	None	N
E/F	0.9628	likely_pathogenic	0.9615	pathogenic	-0.726	Destabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	N
E/G	0.4109	ambiguous	0.4342	ambiguous	-0.941	Destabilizing	0.892	D	0.567	neutral	N	0.468797891	None	None	N
E/H	0.8388	likely_pathogenic	0.8654	pathogenic	-0.931	Destabilizing	0.999	D	0.6	neutral	None	None	None	None	N
E/I	0.8705	likely_pathogenic	0.8721	pathogenic	-0.028	Destabilizing	0.987	D	0.709	prob.delet.	None	None	None	None	N
E/K	0.5865	likely_pathogenic	0.6082	pathogenic	-0.05	Destabilizing	0.892	D	0.547	neutral	N	0.469367322	None	None	N
E/L	0.8188	likely_pathogenic	0.8291	pathogenic	-0.028	Destabilizing	0.987	D	0.705	prob.neutral	None	None	None	None	N
E/M	0.8563	likely_pathogenic	0.8605	pathogenic	0.427	Stabilizing	0.999	D	0.643	neutral	None	None	None	None	N
E/N	0.48	ambiguous	0.5547	ambiguous	-0.334	Destabilizing	0.95	D	0.6	neutral	None	None	None	None	N
E/P	0.9832	likely_pathogenic	0.9847	pathogenic	-0.227	Destabilizing	0.987	D	0.627	neutral	None	None	None	None	N
E/Q	0.3616	ambiguous	0.3902	ambiguous	-0.312	Destabilizing	0.983	D	0.618	neutral	N	0.47407781	None	None	N
E/R	0.7223	likely_pathogenic	0.7425	pathogenic	0.002	Stabilizing	0.987	D	0.625	neutral	None	None	None	None	N
E/S	0.4552	ambiguous	0.5036	ambiguous	-0.559	Destabilizing	0.916	D	0.543	neutral	None	None	None	None	N
E/T	0.5548	ambiguous	0.6001	pathogenic	-0.352	Destabilizing	0.975	D	0.585	neutral	None	None	None	None	N
E/V	0.7126	likely_pathogenic	0.7088	pathogenic	-0.227	Destabilizing	0.983	D	0.667	neutral	N	0.492435554	None	None	N
E/W	0.9852	likely_pathogenic	0.9852	pathogenic	-0.606	Destabilizing	0.999	D	0.723	prob.delet.	None	None	None	None	N
E/Y	0.9237	likely_pathogenic	0.9268	pathogenic	-0.485	Destabilizing	0.999	D	0.66	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.