TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30574	91945;91946;91947	chr2:178550118;178550117;178550116	chr2:179414845;179414844;179414843
N2AB	28933	87022;87023;87024	chr2:178550118;178550117;178550116	chr2:179414845;179414844;179414843
N2A	28006	84241;84242;84243	chr2:178550118;178550117;178550116	chr2:179414845;179414844;179414843
N2B	21509	64750;64751;64752	chr2:178550118;178550117;178550116	chr2:179414845;179414844;179414843
Novex-1	21634	65125;65126;65127	chr2:178550118;178550117;178550116	chr2:179414845;179414844;179414843
Novex-2	21701	65326;65327;65328	chr2:178550118;178550117;178550116	chr2:179414845;179414844;179414843
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: Ig-149
• Domain position: 43
• Structural Position: 122
• Q(SASA): 0.5262
• 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/V	rs1308285808	-0.127	1.0	N	0.759	0.488	0.62634362422	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	1.65508E-04
E/V	rs1308285808	-0.127	1.0	N	0.759	0.488	0.62634362422	gnomAD-4.0.0	2.05259E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	4.96936E-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
E/A	0.3818	ambiguous	0.3982	ambiguous	-0.877	Destabilizing	0.996	D	0.621	neutral	N	0.492213696	None	None	N
E/C	0.9468	likely_pathogenic	0.9476	pathogenic	-0.4	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
E/D	0.1709	likely_benign	0.1794	benign	-0.858	Destabilizing	0.275	N	0.257	neutral	D	0.526170857	None	None	N
E/F	0.9128	likely_pathogenic	0.923	pathogenic	-0.148	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
E/G	0.5037	ambiguous	0.5125	ambiguous	-1.244	Destabilizing	0.998	D	0.669	neutral	D	0.534675697	None	None	N
E/H	0.7615	likely_pathogenic	0.7697	pathogenic	-0.325	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	N
E/I	0.5886	likely_pathogenic	0.6102	pathogenic	0.128	Stabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
E/K	0.584	likely_pathogenic	0.5911	pathogenic	-0.239	Destabilizing	0.992	D	0.525	neutral	N	0.50021362	None	None	N
E/L	0.6876	likely_pathogenic	0.7207	pathogenic	0.128	Stabilizing	0.999	D	0.785	deleterious	None	None	None	None	N
E/M	0.7006	likely_pathogenic	0.721	pathogenic	0.5	Stabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
E/N	0.4972	ambiguous	0.5111	ambiguous	-0.874	Destabilizing	0.998	D	0.66	neutral	None	None	None	None	N
E/P	0.9823	likely_pathogenic	0.9837	pathogenic	-0.186	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
E/Q	0.311	likely_benign	0.3154	benign	-0.728	Destabilizing	0.999	D	0.598	neutral	N	0.503851358	None	None	N
E/R	0.7036	likely_pathogenic	0.7095	pathogenic	0.023	Stabilizing	0.999	D	0.697	prob.neutral	None	None	None	None	N
E/S	0.4529	ambiguous	0.4733	ambiguous	-1.167	Destabilizing	0.994	D	0.577	neutral	None	None	None	None	N
E/T	0.4377	ambiguous	0.4562	ambiguous	-0.842	Destabilizing	0.999	D	0.701	prob.neutral	None	None	None	None	N
E/V	0.3766	ambiguous	0.3949	ambiguous	-0.186	Destabilizing	1.0	D	0.759	deleterious	N	0.479841135	None	None	N
E/W	0.9744	likely_pathogenic	0.9755	pathogenic	0.214	Stabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
E/Y	0.8497	likely_pathogenic	0.8549	pathogenic	0.158	Stabilizing	1.0	D	0.763	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.