TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4870	14833;14834;14835	chr2:178735838;178735837;178735836	chr2:179600565;179600564;179600563
N2AB	4553	13882;13883;13884	chr2:178735838;178735837;178735836	chr2:179600565;179600564;179600563
N2A	3626	11101;11102;11103	chr2:178735838;178735837;178735836	chr2:179600565;179600564;179600563
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Ig-31
• Domain position: 76
• Structural Position: 159
• Q(SASA): 0.265
• 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
S/F	None	None	0.999	D	0.823	0.464	0.769190748641	gnomAD-4.0.0	1.59142E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02499E-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
S/A	0.1078	likely_benign	0.1055	benign	-0.672	Destabilizing	0.973	D	0.513	neutral	N	0.509043974	None	None	N
S/C	0.2264	likely_benign	0.2091	benign	-0.667	Destabilizing	1.0	D	0.75	deleterious	D	0.627168469	None	None	N
S/D	0.8259	likely_pathogenic	0.7778	pathogenic	-0.967	Destabilizing	0.996	D	0.673	neutral	None	None	None	None	N
S/E	0.7792	likely_pathogenic	0.7311	pathogenic	-0.977	Destabilizing	0.996	D	0.67	neutral	None	None	None	None	N
S/F	0.3418	ambiguous	0.3015	benign	-0.948	Destabilizing	0.999	D	0.823	deleterious	D	0.554772329	None	None	N
S/G	0.2032	likely_benign	0.1844	benign	-0.896	Destabilizing	0.996	D	0.589	neutral	None	None	None	None	N
S/H	0.6416	likely_pathogenic	0.5878	pathogenic	-1.419	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
S/I	0.3131	likely_benign	0.2928	benign	-0.183	Destabilizing	0.998	D	0.814	deleterious	None	None	None	None	N
S/K	0.8818	likely_pathogenic	0.8465	pathogenic	-0.83	Destabilizing	0.996	D	0.671	neutral	None	None	None	None	N
S/L	0.172	likely_benign	0.1638	benign	-0.183	Destabilizing	0.992	D	0.699	prob.neutral	None	None	None	None	N
S/M	0.3395	likely_benign	0.3125	benign	0.161	Stabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
S/N	0.3603	ambiguous	0.3148	benign	-0.874	Destabilizing	0.996	D	0.673	neutral	None	None	None	None	N
S/P	0.971	likely_pathogenic	0.971	pathogenic	-0.314	Destabilizing	0.999	D	0.752	deleterious	D	0.687819398	None	None	N
S/Q	0.7144	likely_pathogenic	0.6611	pathogenic	-1.131	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
S/R	0.7994	likely_pathogenic	0.751	pathogenic	-0.618	Destabilizing	0.999	D	0.763	deleterious	None	None	None	None	N
S/T	0.1151	likely_benign	0.1061	benign	-0.816	Destabilizing	0.543	D	0.358	neutral	N	0.490549507	None	None	N
S/V	0.2836	likely_benign	0.2615	benign	-0.314	Destabilizing	0.998	D	0.731	prob.delet.	None	None	None	None	N
S/W	0.5638	ambiguous	0.5369	ambiguous	-0.938	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
S/Y	0.3482	ambiguous	0.3267	benign	-0.652	Destabilizing	0.999	D	0.818	deleterious	D	0.567472252	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.