TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30374	91345;91346;91347	chr2:178551780;178551779;178551778	chr2:179416507;179416506;179416505
N2AB	28733	86422;86423;86424	chr2:178551780;178551779;178551778	chr2:179416507;179416506;179416505
N2A	27806	83641;83642;83643	chr2:178551780;178551779;178551778	chr2:179416507;179416506;179416505
N2B	21309	64150;64151;64152	chr2:178551780;178551779;178551778	chr2:179416507;179416506;179416505
Novex-1	21434	64525;64526;64527	chr2:178551780;178551779;178551778	chr2:179416507;179416506;179416505
Novex-2	21501	64726;64727;64728	chr2:178551780;178551779;178551778	chr2:179416507;179416506;179416505
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-109
• Domain position: 51
• Structural Position: 68
• Q(SASA): 0.2552
• 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
V/I	None	None	0.001	N	0.371	0.075	0.260735089382	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
V/A	0.2063	likely_benign	0.2189	benign	-1.499	Destabilizing	0.001	N	0.391	neutral	N	0.429169093	None	None	N
V/C	0.6604	likely_pathogenic	0.6773	pathogenic	-1.0	Destabilizing	0.909	D	0.682	prob.neutral	None	None	None	None	N
V/D	0.7192	likely_pathogenic	0.7573	pathogenic	-1.292	Destabilizing	0.667	D	0.761	deleterious	N	0.492462007	None	None	N
V/E	0.5912	likely_pathogenic	0.6464	pathogenic	-1.184	Destabilizing	0.567	D	0.703	prob.neutral	None	None	None	None	N
V/F	0.2693	likely_benign	0.3218	benign	-0.965	Destabilizing	0.331	N	0.668	neutral	N	0.464581155	None	None	N
V/G	0.3746	ambiguous	0.4165	ambiguous	-1.927	Destabilizing	0.331	N	0.668	neutral	N	0.484321706	None	None	N
V/H	0.8313	likely_pathogenic	0.8745	pathogenic	-1.498	Destabilizing	0.968	D	0.761	deleterious	None	None	None	None	N
V/I	0.0641	likely_benign	0.067	benign	-0.379	Destabilizing	0.001	N	0.371	neutral	N	0.48719589	None	None	N
V/K	0.8116	likely_pathogenic	0.8536	pathogenic	-1.165	Destabilizing	0.567	D	0.701	prob.neutral	None	None	None	None	N
V/L	0.1426	likely_benign	0.1611	benign	-0.379	Destabilizing	0.001	N	0.278	neutral	N	0.464223029	None	None	N
V/M	0.1388	likely_benign	0.1549	benign	-0.335	Destabilizing	0.567	D	0.591	neutral	None	None	None	None	N
V/N	0.513	ambiguous	0.5767	pathogenic	-1.203	Destabilizing	0.726	D	0.769	deleterious	None	None	None	None	N
V/P	0.8791	likely_pathogenic	0.9063	pathogenic	-0.719	Destabilizing	0.726	D	0.726	prob.delet.	None	None	None	None	N
V/Q	0.6399	likely_pathogenic	0.7026	pathogenic	-1.187	Destabilizing	0.726	D	0.741	deleterious	None	None	None	None	N
V/R	0.7743	likely_pathogenic	0.8241	pathogenic	-0.873	Destabilizing	0.567	D	0.767	deleterious	None	None	None	None	N
V/S	0.35	ambiguous	0.3888	ambiguous	-1.827	Destabilizing	0.396	N	0.647	neutral	None	None	None	None	N
V/T	0.2907	likely_benign	0.3216	benign	-1.58	Destabilizing	0.272	N	0.514	neutral	None	None	None	None	N
V/W	0.8879	likely_pathogenic	0.9203	pathogenic	-1.299	Destabilizing	0.968	D	0.731	prob.delet.	None	None	None	None	N
V/Y	0.6776	likely_pathogenic	0.7375	pathogenic	-0.91	Destabilizing	0.726	D	0.685	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.