TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6937	21034;21035;21036	chr2:178725395;178725394;178725393	chr2:179590122;179590121;179590120
N2AB	6620	20083;20084;20085	chr2:178725395;178725394;178725393	chr2:179590122;179590121;179590120
N2A	5693	17302;17303;17304	chr2:178725395;178725394;178725393	chr2:179590122;179590121;179590120
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-53
• Domain position: 84
• Structural Position: 168
• Q(SASA): 0.3577
• 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/K	None	None	0.238	N	0.195	0.276	0.352476196916	gnomAD-4.0.0	1.64393E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.09349E-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	0.4762	ambiguous	0.4644	ambiguous	-0.646	Destabilizing	0.906	D	0.523	neutral	N	0.503511231	None	None	N
E/C	0.9736	likely_pathogenic	0.974	pathogenic	-0.437	Destabilizing	1.0	D	0.56	neutral	None	None	None	None	N
E/D	0.3618	ambiguous	0.3371	benign	-1.053	Destabilizing	0.979	D	0.493	neutral	N	0.512412001	None	None	N
E/F	0.9565	likely_pathogenic	0.9552	pathogenic	0.124	Stabilizing	0.991	D	0.593	neutral	None	None	None	None	N
E/G	0.4701	ambiguous	0.4779	ambiguous	-1.029	Destabilizing	0.979	D	0.55	neutral	D	0.531276724	None	None	N
E/H	0.8535	likely_pathogenic	0.8491	pathogenic	-0.015	Destabilizing	0.999	D	0.543	neutral	None	None	None	None	N
E/I	0.7759	likely_pathogenic	0.7631	pathogenic	0.402	Stabilizing	0.991	D	0.603	neutral	None	None	None	None	N
E/K	0.4447	ambiguous	0.4465	ambiguous	-0.548	Destabilizing	0.238	N	0.195	neutral	N	0.490633988	None	None	N
E/L	0.8297	likely_pathogenic	0.8296	pathogenic	0.402	Stabilizing	0.969	D	0.558	neutral	None	None	None	None	N
E/M	0.7805	likely_pathogenic	0.7792	pathogenic	0.693	Stabilizing	0.999	D	0.563	neutral	None	None	None	None	N
E/N	0.6666	likely_pathogenic	0.6444	pathogenic	-1.107	Destabilizing	0.984	D	0.503	neutral	None	None	None	None	N
E/P	0.9702	likely_pathogenic	0.9689	pathogenic	0.074	Stabilizing	0.999	D	0.612	neutral	None	None	None	None	N
E/Q	0.2859	likely_benign	0.2851	benign	-0.939	Destabilizing	0.959	D	0.492	neutral	N	0.488685432	None	None	N
E/R	0.6512	likely_pathogenic	0.6686	pathogenic	-0.149	Destabilizing	0.088	N	0.293	neutral	None	None	None	None	N
E/S	0.5061	ambiguous	0.4831	ambiguous	-1.406	Destabilizing	0.939	D	0.518	neutral	None	None	None	None	N
E/T	0.5269	ambiguous	0.5095	ambiguous	-1.086	Destabilizing	0.293	N	0.304	neutral	None	None	None	None	N
E/V	0.5375	ambiguous	0.5252	ambiguous	0.074	Stabilizing	0.959	D	0.545	neutral	N	0.499347402	None	None	N
E/W	0.9743	likely_pathogenic	0.9773	pathogenic	0.393	Stabilizing	0.183	N	0.538	neutral	None	None	None	None	N
E/Y	0.9073	likely_pathogenic	0.9038	pathogenic	0.382	Stabilizing	0.991	D	0.596	neutral	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.