TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26710	80353;80354;80355	chr2:178566004;178566003;178566002	chr2:179430731;179430730;179430729
N2AB	25069	75430;75431;75432	chr2:178566004;178566003;178566002	chr2:179430731;179430730;179430729
N2A	24142	72649;72650;72651	chr2:178566004;178566003;178566002	chr2:179430731;179430730;179430729
N2B	17645	53158;53159;53160	chr2:178566004;178566003;178566002	chr2:179430731;179430730;179430729
Novex-1	17770	53533;53534;53535	chr2:178566004;178566003;178566002	chr2:179430731;179430730;179430729
Novex-2	17837	53734;53735;53736	chr2:178566004;178566003;178566002	chr2:179430731;179430730;179430729
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-82
• Domain position: 28
• Structural Position: 30
• Q(SASA): 0.3364
• 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
D/G	None	None	1.0	D	0.717	0.685	0.418964662724	gnomAD-4.0.0	1.5918E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85938E-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
D/A	0.9293	likely_pathogenic	0.8834	pathogenic	-0.437	Destabilizing	1.0	D	0.725	prob.delet.	N	0.506553791	None	None	I
D/C	0.9848	likely_pathogenic	0.9793	pathogenic	0.006	Stabilizing	1.0	D	0.644	neutral	None	None	None	None	I
D/E	0.8266	likely_pathogenic	0.7832	pathogenic	-0.641	Destabilizing	0.994	D	0.448	neutral	N	0.492537686	None	None	I
D/F	0.9898	likely_pathogenic	0.9845	pathogenic	-0.433	Destabilizing	1.0	D	0.643	neutral	None	None	None	None	I
D/G	0.9247	likely_pathogenic	0.871	pathogenic	-0.709	Destabilizing	1.0	D	0.717	prob.delet.	D	0.523216469	None	None	I
D/H	0.9553	likely_pathogenic	0.9307	pathogenic	-0.715	Destabilizing	1.0	D	0.646	neutral	N	0.518670565	None	None	I
D/I	0.9811	likely_pathogenic	0.97	pathogenic	0.251	Stabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	I
D/K	0.9879	likely_pathogenic	0.9807	pathogenic	-0.049	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
D/L	0.9737	likely_pathogenic	0.9573	pathogenic	0.251	Stabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
D/M	0.9929	likely_pathogenic	0.9868	pathogenic	0.653	Stabilizing	1.0	D	0.634	neutral	None	None	None	None	I
D/N	0.4432	ambiguous	0.3625	ambiguous	-0.361	Destabilizing	1.0	D	0.705	prob.neutral	N	0.470927939	None	None	I
D/P	0.9899	likely_pathogenic	0.9853	pathogenic	0.046	Stabilizing	0.998	D	0.738	prob.delet.	None	None	None	None	I
D/Q	0.9759	likely_pathogenic	0.9591	pathogenic	-0.293	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
D/R	0.9828	likely_pathogenic	0.9722	pathogenic	-0.018	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	I
D/S	0.7256	likely_pathogenic	0.5972	pathogenic	-0.516	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	I
D/T	0.9059	likely_pathogenic	0.8037	pathogenic	-0.302	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
D/V	0.9549	likely_pathogenic	0.9271	pathogenic	0.046	Stabilizing	1.0	D	0.704	prob.neutral	N	0.521949021	None	None	I
D/W	0.9974	likely_pathogenic	0.9963	pathogenic	-0.337	Destabilizing	1.0	D	0.646	neutral	None	None	None	None	I
D/Y	0.9294	likely_pathogenic	0.9076	pathogenic	-0.21	Destabilizing	1.0	D	0.627	neutral	D	0.545929079	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.