TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2546	7861;7862;7863	chr2:178773328;178773327;178773326	chr2:179638055;179638054;179638053
N2AB	2546	7861;7862;7863	chr2:178773328;178773327;178773326	chr2:179638055;179638054;179638053
N2A	2546	7861;7862;7863	chr2:178773328;178773327;178773326	chr2:179638055;179638054;179638053
N2B	2500	7723;7724;7725	chr2:178773328;178773327;178773326	chr2:179638055;179638054;179638053
Novex-1	2500	7723;7724;7725	chr2:178773328;178773327;178773326	chr2:179638055;179638054;179638053
Novex-2	2500	7723;7724;7725	chr2:178773328;178773327;178773326	chr2:179638055;179638054;179638053
Novex-3	2546	7861;7862;7863	chr2:178773328;178773327;178773326	chr2:179638055;179638054;179638053

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-15
• Domain position: 14
• Structural Position: 23
• Q(SASA): 0.3942
• 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	None	None	0.999	N	0.43	0.291	0.202949470691	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
E/A	0.7523	likely_pathogenic	0.8245	pathogenic	-0.359	Destabilizing	0.999	D	0.604	neutral	N	0.515314858	None	None	N
E/C	0.9962	likely_pathogenic	0.9975	pathogenic	None	Stabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
E/D	0.8829	likely_pathogenic	0.9274	pathogenic	-0.414	Destabilizing	0.999	D	0.43	neutral	N	0.495982142	None	None	N
E/F	0.9968	likely_pathogenic	0.9982	pathogenic	-0.236	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
E/G	0.8195	likely_pathogenic	0.863	pathogenic	-0.583	Destabilizing	1.0	D	0.657	neutral	D	0.645127718	None	None	N
E/H	0.9855	likely_pathogenic	0.9917	pathogenic	-0.16	Destabilizing	1.0	D	0.633	neutral	None	None	None	None	N
E/I	0.9525	likely_pathogenic	0.9729	pathogenic	0.202	Stabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
E/K	0.7734	likely_pathogenic	0.84	pathogenic	0.234	Stabilizing	0.999	D	0.577	neutral	N	0.508601681	None	None	N
E/L	0.9767	likely_pathogenic	0.9862	pathogenic	0.202	Stabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
E/M	0.967	likely_pathogenic	0.98	pathogenic	0.345	Stabilizing	1.0	D	0.655	neutral	None	None	None	None	N
E/N	0.9552	likely_pathogenic	0.9754	pathogenic	-0.058	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
E/P	0.9642	likely_pathogenic	0.9778	pathogenic	0.036	Stabilizing	1.0	D	0.653	neutral	None	None	None	None	N
E/Q	0.6898	likely_pathogenic	0.7824	pathogenic	-0.01	Destabilizing	1.0	D	0.611	neutral	D	0.582289623	None	None	N
E/R	0.8962	likely_pathogenic	0.9268	pathogenic	0.405	Stabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
E/S	0.8804	likely_pathogenic	0.9288	pathogenic	-0.233	Destabilizing	0.999	D	0.639	neutral	None	None	None	None	N
E/T	0.9265	likely_pathogenic	0.9555	pathogenic	-0.054	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
E/V	0.8745	likely_pathogenic	0.9212	pathogenic	0.036	Stabilizing	1.0	D	0.697	prob.neutral	N	0.489531362	None	None	N
E/W	0.9991	likely_pathogenic	0.9995	pathogenic	-0.1	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
E/Y	0.9939	likely_pathogenic	0.9967	pathogenic	0.002	Stabilizing	1.0	D	0.681	prob.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.