TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16388	49387;49388;49389	chr2:178614235;178614234;178614233	chr2:179478962;179478961;179478960
N2AB	14747	44464;44465;44466	chr2:178614235;178614234;178614233	chr2:179478962;179478961;179478960
N2A	13820	41683;41684;41685	chr2:178614235;178614234;178614233	chr2:179478962;179478961;179478960
N2B	7323	22192;22193;22194	chr2:178614235;178614234;178614233	chr2:179478962;179478961;179478960
Novex-1	7448	22567;22568;22569	chr2:178614235;178614234;178614233	chr2:179478962;179478961;179478960
Novex-2	7515	22768;22769;22770	chr2:178614235;178614234;178614233	chr2:179478962;179478961;179478960
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: Fn3-6
• Domain position: 38
• Structural Position: 40
• Q(SASA): 0.0808
• 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/M	rs1299253449	-0.433	0.942	D	0.661	0.472	0.675557862682	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.94E-06	0
V/M	rs1299253449	-0.433	0.942	D	0.661	0.472	0.675557862682	gnomAD-3.1.2	6.59E-06	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
V/M	rs1299253449	-0.433	0.942	D	0.661	0.472	0.675557862682	gnomAD-4.0.0	2.56641E-06	None	None	None	None	N	None	1.69497E-05	0	None	0	0	None	0	0	0	0	2.85014E-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
V/A	0.8577	likely_pathogenic	0.8244	pathogenic	-2.134	Highly Destabilizing	0.822	D	0.597	neutral	D	0.73348747	None	None	N
V/C	0.9752	likely_pathogenic	0.9714	pathogenic	-1.4	Destabilizing	0.998	D	0.767	deleterious	None	None	None	None	N
V/D	0.9991	likely_pathogenic	0.9987	pathogenic	-2.953	Highly Destabilizing	0.993	D	0.909	deleterious	None	None	None	None	N
V/E	0.9958	likely_pathogenic	0.9944	pathogenic	-2.599	Highly Destabilizing	0.971	D	0.883	deleterious	D	0.790709672	None	None	N
V/F	0.923	likely_pathogenic	0.9058	pathogenic	-1.134	Destabilizing	0.915	D	0.778	deleterious	None	None	None	None	N
V/G	0.9623	likely_pathogenic	0.954	pathogenic	-2.786	Highly Destabilizing	0.971	D	0.895	deleterious	D	0.790709672	None	None	N
V/H	0.999	likely_pathogenic	0.9987	pathogenic	-2.762	Highly Destabilizing	0.998	D	0.875	deleterious	None	None	None	None	N
V/I	0.0901	likely_benign	0.0892	benign	-0.222	Destabilizing	0.559	D	0.502	neutral	None	None	None	None	N
V/K	0.9967	likely_pathogenic	0.9958	pathogenic	-1.573	Destabilizing	0.978	D	0.881	deleterious	None	None	None	None	N
V/L	0.3977	ambiguous	0.385	ambiguous	-0.222	Destabilizing	0.006	N	0.323	neutral	N	0.500416292	None	None	N
V/M	0.7239	likely_pathogenic	0.692	pathogenic	-0.503	Destabilizing	0.942	D	0.661	neutral	D	0.629314164	None	None	N
V/N	0.9968	likely_pathogenic	0.9957	pathogenic	-2.359	Highly Destabilizing	0.993	D	0.914	deleterious	None	None	None	None	N
V/P	0.9959	likely_pathogenic	0.9942	pathogenic	-0.842	Destabilizing	0.993	D	0.898	deleterious	None	None	None	None	N
V/Q	0.9952	likely_pathogenic	0.9939	pathogenic	-1.896	Destabilizing	0.993	D	0.907	deleterious	None	None	None	None	N
V/R	0.9936	likely_pathogenic	0.9913	pathogenic	-1.924	Destabilizing	0.978	D	0.914	deleterious	None	None	None	None	N
V/S	0.9852	likely_pathogenic	0.9801	pathogenic	-2.86	Highly Destabilizing	0.978	D	0.867	deleterious	None	None	None	None	N
V/T	0.9049	likely_pathogenic	0.8878	pathogenic	-2.325	Highly Destabilizing	0.86	D	0.596	neutral	None	None	None	None	N
V/W	0.9988	likely_pathogenic	0.9985	pathogenic	-1.637	Destabilizing	0.998	D	0.855	deleterious	None	None	None	None	N
V/Y	0.9959	likely_pathogenic	0.9941	pathogenic	-1.321	Destabilizing	0.978	D	0.779	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.