TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30361	91306;91307;91308	chr2:178551819;178551818;178551817	chr2:179416546;179416545;179416544
N2AB	28720	86383;86384;86385	chr2:178551819;178551818;178551817	chr2:179416546;179416545;179416544
N2A	27793	83602;83603;83604	chr2:178551819;178551818;178551817	chr2:179416546;179416545;179416544
N2B	21296	64111;64112;64113	chr2:178551819;178551818;178551817	chr2:179416546;179416545;179416544
Novex-1	21421	64486;64487;64488	chr2:178551819;178551818;178551817	chr2:179416546;179416545;179416544
Novex-2	21488	64687;64688;64689	chr2:178551819;178551818;178551817	chr2:179416546;179416545;179416544
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: 38
• Structural Position: 40
• Q(SASA): 0.0998
• 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	rs1237357912	-2.958	0.996	D	0.593	0.578	0.699720955005	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	1.3925E-04	0	0
V/A	rs1237357912	-2.958	0.996	D	0.593	0.578	0.699720955005	gnomAD-4.0.0	3.18228E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.76492E-05	0	0	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	0.612	likely_pathogenic	0.6177	pathogenic	-2.465	Highly Destabilizing	0.996	D	0.593	neutral	D	0.54707312	None	None	N
V/C	0.8994	likely_pathogenic	0.907	pathogenic	-1.642	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
V/D	0.9982	likely_pathogenic	0.9979	pathogenic	-3.315	Highly Destabilizing	1.0	D	0.895	deleterious	D	0.547833589	None	None	N
V/E	0.9923	likely_pathogenic	0.991	pathogenic	-3.005	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
V/F	0.7208	likely_pathogenic	0.7319	pathogenic	-1.429	Destabilizing	0.998	D	0.821	deleterious	D	0.547580099	None	None	N
V/G	0.8956	likely_pathogenic	0.8898	pathogenic	-3.015	Highly Destabilizing	1.0	D	0.895	deleterious	D	0.547833589	None	None	N
V/H	0.997	likely_pathogenic	0.9968	pathogenic	-2.849	Highly Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
V/I	0.0716	likely_benign	0.0722	benign	-0.83	Destabilizing	0.962	D	0.561	neutral	N	0.443218613	None	None	N
V/K	0.9939	likely_pathogenic	0.993	pathogenic	-2.007	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
V/L	0.2206	likely_benign	0.2265	benign	-0.83	Destabilizing	0.275	N	0.314	neutral	N	0.494247653	None	None	N
V/M	0.3481	ambiguous	0.3549	ambiguous	-1.101	Destabilizing	0.998	D	0.723	prob.delet.	None	None	None	None	N
V/N	0.992	likely_pathogenic	0.9909	pathogenic	-2.762	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
V/P	0.991	likely_pathogenic	0.9874	pathogenic	-1.363	Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
V/Q	0.989	likely_pathogenic	0.9873	pathogenic	-2.375	Highly Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
V/R	0.9883	likely_pathogenic	0.9867	pathogenic	-2.162	Highly Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	N
V/S	0.9447	likely_pathogenic	0.9409	pathogenic	-3.128	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
V/T	0.7687	likely_pathogenic	0.7598	pathogenic	-2.673	Highly Destabilizing	0.997	D	0.63	neutral	None	None	None	None	N
V/W	0.9937	likely_pathogenic	0.9942	pathogenic	-1.849	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
V/Y	0.9799	likely_pathogenic	0.9791	pathogenic	-1.673	Destabilizing	1.0	D	0.82	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.