TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20764	62515;62516;62517	chr2:178589435;178589434;178589433	chr2:179454162;179454161;179454160
N2AB	19123	57592;57593;57594	chr2:178589435;178589434;178589433	chr2:179454162;179454161;179454160
N2A	18196	54811;54812;54813	chr2:178589435;178589434;178589433	chr2:179454162;179454161;179454160
N2B	11699	35320;35321;35322	chr2:178589435;178589434;178589433	chr2:179454162;179454161;179454160
Novex-1	11824	35695;35696;35697	chr2:178589435;178589434;178589433	chr2:179454162;179454161;179454160
Novex-2	11891	35896;35897;35898	chr2:178589435;178589434;178589433	chr2:179454162;179454161;179454160
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: Fn3-38
• Domain position: 97
• Structural Position: 131
• Q(SASA): 0.5841
• 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/Q	rs397517651	-0.259	0.999	N	0.649	0.298	None	gnomAD-2.1.1	1.43E-05	None	None	None	None	N	None	1.65344E-04	0	None	0	0	None	0	None	0	0	0
E/Q	rs397517651	-0.259	0.999	N	0.649	0.298	None	gnomAD-3.1.2	6.58E-05	None	None	None	None	N	None	2.41371E-04	0	0	0	0	None	0	0	0	0	0
E/Q	rs397517651	-0.259	0.999	N	0.649	0.298	None	gnomAD-4.0.0	1.11574E-05	None	None	None	None	N	None	2.40359E-04	0	None	0	0	None	0	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
E/A	0.5825	likely_pathogenic	0.5672	pathogenic	-0.695	Destabilizing	0.983	D	0.493	neutral	N	0.496834093	None	None	N
E/C	0.9881	likely_pathogenic	0.9901	pathogenic	-0.38	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
E/D	0.2015	likely_benign	0.2046	benign	-0.598	Destabilizing	0.991	D	0.511	neutral	N	0.434881557	None	None	N
E/F	0.9878	likely_pathogenic	0.9887	pathogenic	-0.275	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
E/G	0.5773	likely_pathogenic	0.5709	pathogenic	-0.971	Destabilizing	0.991	D	0.596	neutral	N	0.479545085	None	None	N
E/H	0.9568	likely_pathogenic	0.9534	pathogenic	-0.265	Destabilizing	1.0	D	0.568	neutral	None	None	None	None	N
E/I	0.9253	likely_pathogenic	0.9285	pathogenic	0.032	Stabilizing	0.999	D	0.769	deleterious	None	None	None	None	N
E/K	0.8079	likely_pathogenic	0.7854	pathogenic	-0.255	Destabilizing	0.991	D	0.503	neutral	N	0.478531127	None	None	N
E/L	0.9107	likely_pathogenic	0.9016	pathogenic	0.032	Stabilizing	0.999	D	0.667	prob.neutral	None	None	None	None	N
E/M	0.9236	likely_pathogenic	0.9154	pathogenic	0.225	Stabilizing	1.0	D	0.707	prob.delet.	None	None	None	None	N
E/N	0.7338	likely_pathogenic	0.7006	pathogenic	-0.629	Destabilizing	0.998	D	0.667	prob.neutral	None	None	None	None	N
E/P	0.8927	likely_pathogenic	0.8595	pathogenic	-0.19	Destabilizing	0.999	D	0.661	prob.neutral	None	None	None	None	N
E/Q	0.6366	likely_pathogenic	0.5919	pathogenic	-0.55	Destabilizing	0.999	D	0.649	prob.neutral	N	0.467517216	None	None	N
E/R	0.8948	likely_pathogenic	0.8767	pathogenic	0.066	Stabilizing	0.999	D	0.611	neutral	None	None	None	None	N
E/S	0.7112	likely_pathogenic	0.697	pathogenic	-0.862	Destabilizing	0.854	D	0.327	neutral	None	None	None	None	N
E/T	0.7865	likely_pathogenic	0.7672	pathogenic	-0.639	Destabilizing	0.987	D	0.659	prob.neutral	None	None	None	None	N
E/V	0.7957	likely_pathogenic	0.7926	pathogenic	-0.19	Destabilizing	0.999	D	0.677	prob.neutral	N	0.480559043	None	None	N
E/W	0.9938	likely_pathogenic	0.9941	pathogenic	-0.031	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
E/Y	0.9701	likely_pathogenic	0.9708	pathogenic	-0.036	Destabilizing	1.0	D	0.717	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.