TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19286	58081;58082;58083	chr2:178594638;178594637;178594636	chr2:179459365;179459364;179459363
N2AB	17645	53158;53159;53160	chr2:178594638;178594637;178594636	chr2:179459365;179459364;179459363
N2A	16718	50377;50378;50379	chr2:178594638;178594637;178594636	chr2:179459365;179459364;179459363
N2B	10221	30886;30887;30888	chr2:178594638;178594637;178594636	chr2:179459365;179459364;179459363
Novex-1	10346	31261;31262;31263	chr2:178594638;178594637;178594636	chr2:179459365;179459364;179459363
Novex-2	10413	31462;31463;31464	chr2:178594638;178594637;178594636	chr2:179459365;179459364;179459363
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-28
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.1589
• 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/K	rs558844442	-1.478	0.939	N	0.523	0.267	0.389439708392	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.93723E-04	None	0	0	0	0	0
E/K	rs558844442	-1.478	0.939	N	0.523	0.267	0.389439708392	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	1E-03	0	None	None	None	0	None
E/K	rs558844442	-1.478	0.939	N	0.523	0.267	0.389439708392	gnomAD-4.0.0	6.57289E-06	None	None	None	None	N	None	0	0	None	0	1.94175E-04	None	0	0	0	0	0
E/Q	rs558844442	-1.521	0.991	N	0.569	0.24	0.313210971179	gnomAD-2.1.1	4.24E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.25E-06	0
E/Q	rs558844442	-1.521	0.991	N	0.569	0.24	0.313210971179	gnomAD-4.0.0	2.76979E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.81238E-06	1.1976E-05	1.67977E-05

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	0.5008	ambiguous	0.4927	ambiguous	-0.856	Destabilizing	0.939	D	0.495	neutral	N	0.475167955	None	None	N
E/C	0.9644	likely_pathogenic	0.9662	pathogenic	-0.562	Destabilizing	0.999	D	0.766	deleterious	None	None	None	None	N
E/D	0.1725	likely_benign	0.1727	benign	-1.177	Destabilizing	0.046	N	0.318	neutral	N	0.380254852	None	None	N
E/F	0.9704	likely_pathogenic	0.9735	pathogenic	-0.122	Destabilizing	0.998	D	0.8	deleterious	None	None	None	None	N
E/G	0.3357	likely_benign	0.3445	ambiguous	-1.281	Destabilizing	0.046	N	0.419	neutral	N	0.343120616	None	None	N
E/H	0.8987	likely_pathogenic	0.9084	pathogenic	-0.519	Destabilizing	0.999	D	0.568	neutral	None	None	None	None	N
E/I	0.9286	likely_pathogenic	0.9334	pathogenic	0.329	Stabilizing	0.993	D	0.813	deleterious	None	None	None	None	N
E/K	0.7077	likely_pathogenic	0.7389	pathogenic	-0.982	Destabilizing	0.939	D	0.523	neutral	N	0.474994597	None	None	N
E/L	0.8453	likely_pathogenic	0.8513	pathogenic	0.329	Stabilizing	0.993	D	0.78	deleterious	None	None	None	None	N
E/M	0.8743	likely_pathogenic	0.8927	pathogenic	0.819	Stabilizing	0.999	D	0.739	prob.delet.	None	None	None	None	N
E/N	0.6289	likely_pathogenic	0.6334	pathogenic	-1.402	Destabilizing	0.973	D	0.571	neutral	None	None	None	None	N
E/P	0.9744	likely_pathogenic	0.9799	pathogenic	-0.046	Destabilizing	0.993	D	0.657	neutral	None	None	None	None	N
E/Q	0.4394	ambiguous	0.4712	ambiguous	-1.188	Destabilizing	0.991	D	0.569	neutral	N	0.499506252	None	None	N
E/R	0.8224	likely_pathogenic	0.8352	pathogenic	-0.734	Destabilizing	0.993	D	0.573	neutral	None	None	None	None	N
E/S	0.4982	ambiguous	0.4952	ambiguous	-1.851	Destabilizing	0.953	D	0.479	neutral	None	None	None	None	N
E/T	0.709	likely_pathogenic	0.724	pathogenic	-1.491	Destabilizing	0.993	D	0.608	neutral	None	None	None	None	N
E/V	0.8077	likely_pathogenic	0.8148	pathogenic	-0.046	Destabilizing	0.991	D	0.717	prob.delet.	N	0.519401522	None	None	N
E/W	0.987	likely_pathogenic	0.9888	pathogenic	0.069	Stabilizing	0.999	D	0.73	prob.delet.	None	None	None	None	N
E/Y	0.9392	likely_pathogenic	0.9445	pathogenic	0.112	Stabilizing	0.998	D	0.758	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.