TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17507	52744;52745;52746	chr2:178608364;178608363;178608362	chr2:179473091;179473090;179473089
N2AB	15866	47821;47822;47823	chr2:178608364;178608363;178608362	chr2:179473091;179473090;179473089
N2A	14939	45040;45041;45042	chr2:178608364;178608363;178608362	chr2:179473091;179473090;179473089
N2B	8442	25549;25550;25551	chr2:178608364;178608363;178608362	chr2:179473091;179473090;179473089
Novex-1	8567	25924;25925;25926	chr2:178608364;178608363;178608362	chr2:179473091;179473090;179473089
Novex-2	8634	26125;26126;26127	chr2:178608364;178608363;178608362	chr2:179473091;179473090;179473089
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: Fn3-15
• Domain position: 38
• Structural Position: 41
• Q(SASA): 0.0857
• 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	None	None	1.0	D	0.751	0.564	0.481690325388	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	0.9805	likely_pathogenic	0.978	pathogenic	-0.944	Destabilizing	0.999	D	0.686	prob.neutral	N	0.519885106	None	None	N
E/C	0.9952	likely_pathogenic	0.9942	pathogenic	-0.044	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
E/D	0.9623	likely_pathogenic	0.9465	pathogenic	-1.489	Destabilizing	0.999	D	0.649	neutral	N	0.479157146	None	None	N
E/F	0.9979	likely_pathogenic	0.9972	pathogenic	-0.648	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
E/G	0.982	likely_pathogenic	0.9789	pathogenic	-1.347	Destabilizing	1.0	D	0.751	deleterious	D	0.526432473	None	None	N
E/H	0.993	likely_pathogenic	0.99	pathogenic	-0.458	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
E/I	0.995	likely_pathogenic	0.9933	pathogenic	0.209	Stabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
E/K	0.9864	likely_pathogenic	0.9819	pathogenic	-0.656	Destabilizing	0.999	D	0.669	neutral	N	0.489157098	None	None	N
E/L	0.993	likely_pathogenic	0.9906	pathogenic	0.209	Stabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/M	0.9916	likely_pathogenic	0.989	pathogenic	0.834	Stabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
E/N	0.996	likely_pathogenic	0.9951	pathogenic	-1.003	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
E/P	0.9999	likely_pathogenic	0.9998	pathogenic	-0.16	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
E/Q	0.8588	likely_pathogenic	0.8426	pathogenic	-0.682	Destabilizing	1.0	D	0.746	deleterious	N	0.468241686	None	None	N
E/R	0.988	likely_pathogenic	0.9827	pathogenic	-0.658	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
E/S	0.9831	likely_pathogenic	0.9821	pathogenic	-1.584	Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	N
E/T	0.9926	likely_pathogenic	0.9923	pathogenic	-1.184	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
E/V	0.9871	likely_pathogenic	0.9827	pathogenic	-0.16	Destabilizing	1.0	D	0.75	deleterious	D	0.525418514	None	None	N
E/W	0.9986	likely_pathogenic	0.9979	pathogenic	-0.775	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
E/Y	0.996	likely_pathogenic	0.9948	pathogenic	-0.412	Destabilizing	1.0	D	0.782	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.