TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18876	56851;56852;56853	chr2:178599167;178599166;178599165	chr2:179463894;179463893;179463892
N2AB	17235	51928;51929;51930	chr2:178599167;178599166;178599165	chr2:179463894;179463893;179463892
N2A	16308	49147;49148;49149	chr2:178599167;178599166;178599165	chr2:179463894;179463893;179463892
N2B	9811	29656;29657;29658	chr2:178599167;178599166;178599165	chr2:179463894;179463893;179463892
Novex-1	9936	30031;30032;30033	chr2:178599167;178599166;178599165	chr2:179463894;179463893;179463892
Novex-2	10003	30232;30233;30234	chr2:178599167;178599166;178599165	chr2:179463894;179463893;179463892
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-24
• Domain position: 93
• Structural Position: 127
• Q(SASA): 0.1756
• 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
E/G	rs2052624292	None	0.976	N	0.615	0.191	0.299427821978	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/G	rs2052624292	None	0.976	N	0.615	0.191	0.299427821978	gnomAD-4.0.0	6.57419E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47067E-05	0	0
E/K	rs919241154	None	0.954	N	0.481	0.185	0.256793551483	gnomAD-4.0.0	3.69056E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.70007E-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
E/A	0.1912	likely_benign	0.195	benign	-0.377	Destabilizing	0.954	D	0.515	neutral	N	0.50162105	None	None	N
E/C	0.7432	likely_pathogenic	0.7163	pathogenic	-0.35	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
E/D	0.5583	ambiguous	0.6091	pathogenic	-1.103	Destabilizing	0.976	D	0.449	neutral	N	0.503007917	None	None	N
E/F	0.7928	likely_pathogenic	0.7888	pathogenic	0.467	Stabilizing	0.999	D	0.747	deleterious	None	None	None	None	N
E/G	0.4194	ambiguous	0.4319	ambiguous	-0.772	Destabilizing	0.976	D	0.615	neutral	N	0.484248798	None	None	N
E/H	0.6379	likely_pathogenic	0.6306	pathogenic	0.354	Stabilizing	0.997	D	0.595	neutral	None	None	None	None	N
E/I	0.2789	likely_benign	0.2787	benign	0.702	Stabilizing	0.997	D	0.76	deleterious	None	None	None	None	N
E/K	0.2155	likely_benign	0.2035	benign	-0.295	Destabilizing	0.954	D	0.481	neutral	N	0.5026612	None	None	N
E/L	0.4489	ambiguous	0.4471	ambiguous	0.702	Stabilizing	0.997	D	0.699	prob.delet.	None	None	None	None	N
E/M	0.4151	ambiguous	0.3958	ambiguous	0.899	Stabilizing	1.0	D	0.669	prob.neutral	None	None	None	None	N
E/N	0.6339	likely_pathogenic	0.6425	pathogenic	-0.971	Destabilizing	0.995	D	0.629	neutral	None	None	None	None	N
E/P	0.9781	likely_pathogenic	0.983	pathogenic	0.365	Stabilizing	0.997	D	0.662	prob.neutral	None	None	None	None	N
E/Q	0.1483	likely_benign	0.1425	benign	-0.764	Destabilizing	0.787	D	0.315	neutral	N	0.5026612	None	None	N
E/R	0.362	ambiguous	0.3384	benign	0.074	Stabilizing	0.995	D	0.606	neutral	None	None	None	None	N
E/S	0.4189	ambiguous	0.435	ambiguous	-1.243	Destabilizing	0.679	D	0.351	neutral	None	None	None	None	N
E/T	0.294	likely_benign	0.2879	benign	-0.896	Destabilizing	0.965	D	0.62	neutral	None	None	None	None	N
E/V	0.1521	likely_benign	0.1456	benign	0.365	Stabilizing	0.997	D	0.634	neutral	N	0.387698112	None	None	N
E/W	0.9514	likely_pathogenic	0.9539	pathogenic	0.726	Stabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
E/Y	0.7308	likely_pathogenic	0.7187	pathogenic	0.742	Stabilizing	0.999	D	0.714	prob.delet.	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.