TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15712	47359;47360;47361	chr2:178618324;178618323;178618322	chr2:179483051;179483050;179483049
N2AB	14071	42436;42437;42438	chr2:178618324;178618323;178618322	chr2:179483051;179483050;179483049
N2A	13144	39655;39656;39657	chr2:178618324;178618323;178618322	chr2:179483051;179483050;179483049
N2B	6647	20164;20165;20166	chr2:178618324;178618323;178618322	chr2:179483051;179483050;179483049
Novex-1	6772	20539;20540;20541	chr2:178618324;178618323;178618322	chr2:179483051;179483050;179483049
Novex-2	6839	20740;20741;20742	chr2:178618324;178618323;178618322	chr2:179483051;179483050;179483049
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: Fn3-1
• Domain position: 56
• Structural Position: 83
• Q(SASA): 0.9594
• 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	None	None	0.22	N	0.509	0.168	0.282575091529	gnomAD-4.0.0	2.73843E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59955E-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	0.1844	likely_benign	0.209	benign	-0.048	Destabilizing	0.22	N	0.539	neutral	N	0.465654903	None	None	N
E/C	0.8071	likely_pathogenic	0.8382	pathogenic	-0.1	Destabilizing	0.968	D	0.633	neutral	None	None	None	None	N
E/D	0.0603	likely_benign	0.0606	benign	-0.29	Destabilizing	None	N	0.165	neutral	N	0.407128852	None	None	N
E/F	0.7013	likely_pathogenic	0.7618	pathogenic	-0.048	Destabilizing	0.89	D	0.575	neutral	None	None	None	None	N
E/G	0.1639	likely_benign	0.1926	benign	-0.167	Destabilizing	0.22	N	0.509	neutral	N	0.452681255	None	None	N
E/H	0.4747	ambiguous	0.5307	ambiguous	0.486	Stabilizing	0.726	D	0.55	neutral	None	None	None	None	N
E/I	0.4242	ambiguous	0.4867	ambiguous	0.21	Stabilizing	0.726	D	0.563	neutral	None	None	None	None	N
E/K	0.2528	likely_benign	0.2663	benign	0.518	Stabilizing	0.22	N	0.515	neutral	N	0.427853064	None	None	N
E/L	0.411	ambiguous	0.4792	ambiguous	0.21	Stabilizing	0.567	D	0.557	neutral	None	None	None	None	N
E/M	0.576	likely_pathogenic	0.6253	pathogenic	0.056	Stabilizing	0.968	D	0.577	neutral	None	None	None	None	N
E/N	0.1683	likely_benign	0.1961	benign	0.198	Stabilizing	0.157	N	0.506	neutral	None	None	None	None	N
E/P	0.4056	ambiguous	0.4647	ambiguous	0.142	Stabilizing	0.726	D	0.533	neutral	None	None	None	None	N
E/Q	0.2206	likely_benign	0.2402	benign	0.221	Stabilizing	0.22	N	0.474	neutral	N	0.470538038	None	None	N
E/R	0.3532	ambiguous	0.391	ambiguous	0.696	Stabilizing	0.567	D	0.535	neutral	None	None	None	None	N
E/S	0.1637	likely_benign	0.1933	benign	0.091	Stabilizing	0.157	N	0.501	neutral	None	None	None	None	N
E/T	0.2358	likely_benign	0.2651	benign	0.201	Stabilizing	0.272	N	0.519	neutral	None	None	None	None	N
E/V	0.2649	likely_benign	0.2943	benign	0.142	Stabilizing	0.667	D	0.515	neutral	N	0.477398214	None	None	N
E/W	0.8697	likely_pathogenic	0.8887	pathogenic	0.016	Stabilizing	0.968	D	0.662	neutral	None	None	None	None	N
E/Y	0.5426	ambiguous	0.5802	pathogenic	0.18	Stabilizing	0.89	D	0.571	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.