TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17795	53608;53609;53610	chr2:178607219;178607218;178607217	chr2:179471946;179471945;179471944
N2AB	16154	48685;48686;48687	chr2:178607219;178607218;178607217	chr2:179471946;179471945;179471944
N2A	15227	45904;45905;45906	chr2:178607219;178607218;178607217	chr2:179471946;179471945;179471944
N2B	8730	26413;26414;26415	chr2:178607219;178607218;178607217	chr2:179471946;179471945;179471944
Novex-1	8855	26788;26789;26790	chr2:178607219;178607218;178607217	chr2:179471946;179471945;179471944
Novex-2	8922	26989;26990;26991	chr2:178607219;178607218;178607217	chr2:179471946;179471945;179471944
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: Fn3-17
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.7873
• Predicted PPI site: I

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/D	rs1447853975	None	None	N	0.149	0.072	0.0611884634855	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/D	rs1447853975	None	None	N	0.149	0.072	0.0611884634855	gnomAD-4.0.0	6.57825E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.47154E-05	0	0
E/K	None	None	0.22	N	0.579	0.246	0.243972157842	gnomAD-4.0.0	6.16065E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	7.19831E-06	0	1.65777E-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	0.2674	likely_benign	0.2596	benign	-0.355	Destabilizing	0.22	N	0.632	neutral	N	0.455702334	None	None	I
E/C	0.8634	likely_pathogenic	0.8833	pathogenic	0.057	Stabilizing	0.968	D	0.75	deleterious	None	None	None	None	I
E/D	0.0772	likely_benign	0.0894	benign	-0.263	Destabilizing	None	N	0.149	neutral	N	0.419088172	None	None	I
E/F	0.8529	likely_pathogenic	0.8682	pathogenic	-0.273	Destabilizing	0.89	D	0.697	prob.neutral	None	None	None	None	I
E/G	0.3131	likely_benign	0.3072	benign	-0.54	Destabilizing	0.22	N	0.625	neutral	N	0.48592924	None	None	I
E/H	0.6732	likely_pathogenic	0.6768	pathogenic	-0.055	Destabilizing	0.726	D	0.544	neutral	None	None	None	None	I
E/I	0.5713	likely_pathogenic	0.5514	ambiguous	0.095	Stabilizing	0.726	D	0.699	prob.neutral	None	None	None	None	I
E/K	0.422	ambiguous	0.3658	ambiguous	0.435	Stabilizing	0.22	N	0.579	neutral	N	0.44548534	None	None	I
E/L	0.5866	likely_pathogenic	0.5905	pathogenic	0.095	Stabilizing	0.567	D	0.674	neutral	None	None	None	None	I
E/M	0.7098	likely_pathogenic	0.6815	pathogenic	0.23	Stabilizing	0.968	D	0.685	prob.neutral	None	None	None	None	I
E/N	0.2978	likely_benign	0.3021	benign	0.099	Stabilizing	0.157	N	0.556	neutral	None	None	None	None	I
E/P	0.3811	ambiguous	0.47	ambiguous	-0.035	Destabilizing	0.726	D	0.582	neutral	None	None	None	None	I
E/Q	0.3255	likely_benign	0.295	benign	0.141	Stabilizing	0.22	N	0.508	neutral	N	0.459916075	None	None	I
E/R	0.5463	ambiguous	0.5211	ambiguous	0.576	Stabilizing	0.567	D	0.551	neutral	None	None	None	None	I
E/S	0.306	likely_benign	0.3008	benign	-0.044	Destabilizing	0.157	N	0.567	neutral	None	None	None	None	I
E/T	0.4029	ambiguous	0.3813	ambiguous	0.113	Stabilizing	0.272	N	0.594	neutral	None	None	None	None	I
E/V	0.3815	ambiguous	0.3485	ambiguous	-0.035	Destabilizing	0.667	D	0.617	neutral	N	0.489718907	None	None	I
E/W	0.9459	likely_pathogenic	0.9543	pathogenic	-0.134	Destabilizing	0.968	D	0.767	deleterious	None	None	None	None	I
E/Y	0.7242	likely_pathogenic	0.7528	pathogenic	-0.031	Destabilizing	0.89	D	0.687	prob.neutral	None	None	None	None	I

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.