TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23100	69523;69524;69525	chr2:178577037;178577036;178577035	chr2:179441764;179441763;179441762
N2AB	21459	64600;64601;64602	chr2:178577037;178577036;178577035	chr2:179441764;179441763;179441762
N2A	20532	61819;61820;61821	chr2:178577037;178577036;178577035	chr2:179441764;179441763;179441762
N2B	14035	42328;42329;42330	chr2:178577037;178577036;178577035	chr2:179441764;179441763;179441762
Novex-1	14160	42703;42704;42705	chr2:178577037;178577036;178577035	chr2:179441764;179441763;179441762
Novex-2	14227	42904;42905;42906	chr2:178577037;178577036;178577035	chr2:179441764;179441763;179441762
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-55
• Domain position: 61
• Structural Position: 92
• Q(SASA): 0.4086
• 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/A	None	None	0.014	N	0.231	0.142	0.434045841721	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	0.2406	likely_benign	0.2406	benign	-1.081	Destabilizing	0.014	N	0.231	neutral	N	0.493103142	None	None	N
V/C	0.7947	likely_pathogenic	0.7697	pathogenic	-0.622	Destabilizing	0.994	D	0.677	prob.neutral	None	None	None	None	N
V/D	0.5913	likely_pathogenic	0.6239	pathogenic	-1.077	Destabilizing	0.978	D	0.753	deleterious	None	None	None	None	N
V/E	0.4414	ambiguous	0.4862	ambiguous	-1.157	Destabilizing	0.942	D	0.664	neutral	N	0.489004044	None	None	N
V/F	0.2742	likely_benign	0.264	benign	-1.064	Destabilizing	0.978	D	0.692	prob.neutral	None	None	None	None	N
V/G	0.3756	ambiguous	0.3573	ambiguous	-1.301	Destabilizing	0.698	D	0.668	neutral	N	0.477080004	None	None	N
V/H	0.6598	likely_pathogenic	0.6525	pathogenic	-0.888	Destabilizing	0.043	N	0.502	neutral	None	None	None	None	N
V/I	0.0765	likely_benign	0.0723	benign	-0.615	Destabilizing	0.86	D	0.501	neutral	None	None	None	None	N
V/K	0.5037	ambiguous	0.533	ambiguous	-0.998	Destabilizing	0.956	D	0.674	neutral	None	None	None	None	N
V/L	0.2759	likely_benign	0.2466	benign	-0.615	Destabilizing	0.489	N	0.512	neutral	N	0.466532616	None	None	N
V/M	0.1558	likely_benign	0.1484	benign	-0.384	Destabilizing	0.99	D	0.551	neutral	N	0.468330591	None	None	N
V/N	0.3595	ambiguous	0.3203	benign	-0.646	Destabilizing	0.956	D	0.764	deleterious	None	None	None	None	N
V/P	0.7137	likely_pathogenic	0.689	pathogenic	-0.736	Destabilizing	0.978	D	0.739	prob.delet.	None	None	None	None	N
V/Q	0.4063	ambiguous	0.4077	ambiguous	-0.915	Destabilizing	0.978	D	0.742	deleterious	None	None	None	None	N
V/R	0.496	ambiguous	0.5169	ambiguous	-0.374	Destabilizing	0.978	D	0.767	deleterious	None	None	None	None	N
V/S	0.2844	likely_benign	0.2638	benign	-1.011	Destabilizing	0.754	D	0.632	neutral	None	None	None	None	N
V/T	0.152	likely_benign	0.1538	benign	-0.998	Destabilizing	0.86	D	0.469	neutral	None	None	None	None	N
V/W	0.8759	likely_pathogenic	0.8634	pathogenic	-1.188	Destabilizing	0.998	D	0.757	deleterious	None	None	None	None	N
V/Y	0.6728	likely_pathogenic	0.6662	pathogenic	-0.923	Destabilizing	0.956	D	0.682	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.