TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17325	52198;52199;52200	chr2:178609337;178609336;178609335	chr2:179474064;179474063;179474062
N2AB	15684	47275;47276;47277	chr2:178609337;178609336;178609335	chr2:179474064;179474063;179474062
N2A	14757	44494;44495;44496	chr2:178609337;178609336;178609335	chr2:179474064;179474063;179474062
N2B	8260	25003;25004;25005	chr2:178609337;178609336;178609335	chr2:179474064;179474063;179474062
Novex-1	8385	25378;25379;25380	chr2:178609337;178609336;178609335	chr2:179474064;179474063;179474062
Novex-2	8452	25579;25580;25581	chr2:178609337;178609336;178609335	chr2:179474064;179474063;179474062
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-112
• Domain position: 75
• Structural Position: 125
• Q(SASA): 0.3861
• 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
D/N	rs375717318	-0.271	0.001	N	0.286	0.116	None	gnomAD-2.1.1	4.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.96E-06	0
D/N	rs375717318	-0.271	0.001	N	0.286	0.116	None	gnomAD-4.0.0	2.05752E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.70173E-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	0.3026	likely_benign	0.4187	ambiguous	-0.151	Destabilizing	0.334	N	0.721	prob.delet.	N	0.489575339	None	None	N
D/C	0.6037	likely_pathogenic	0.7049	pathogenic	0.444	Stabilizing	0.982	D	0.826	deleterious	None	None	None	None	N
D/E	0.2515	likely_benign	0.3179	benign	-0.274	Destabilizing	0.201	N	0.573	neutral	N	0.415154938	None	None	N
D/F	0.6459	likely_pathogenic	0.7482	pathogenic	-0.525	Destabilizing	0.982	D	0.838	deleterious	None	None	None	None	N
D/G	0.4041	ambiguous	0.519	ambiguous	-0.302	Destabilizing	0.201	N	0.626	neutral	N	0.487999258	None	None	N
D/H	0.3083	likely_benign	0.403	ambiguous	-0.625	Destabilizing	0.869	D	0.777	deleterious	N	0.506507661	None	None	N
D/I	0.3869	ambiguous	0.476	ambiguous	0.182	Stabilizing	0.826	D	0.858	deleterious	None	None	None	None	N
D/K	0.4944	ambiguous	0.5821	pathogenic	0.573	Stabilizing	0.539	D	0.727	prob.delet.	None	None	None	None	N
D/L	0.4613	ambiguous	0.5823	pathogenic	0.182	Stabilizing	0.7	D	0.818	deleterious	None	None	None	None	N
D/M	0.6734	likely_pathogenic	0.7533	pathogenic	0.52	Stabilizing	0.982	D	0.833	deleterious	None	None	None	None	N
D/N	0.0982	likely_benign	0.129	benign	0.463	Stabilizing	0.001	N	0.286	neutral	N	0.493674437	None	None	N
D/P	0.9159	likely_pathogenic	0.9443	pathogenic	0.092	Stabilizing	0.826	D	0.765	deleterious	None	None	None	None	N
D/Q	0.4069	ambiguous	0.5142	ambiguous	0.439	Stabilizing	0.7	D	0.693	prob.neutral	None	None	None	None	N
D/R	0.4668	ambiguous	0.5667	pathogenic	0.432	Stabilizing	0.7	D	0.773	deleterious	None	None	None	None	N
D/S	0.1759	likely_benign	0.2356	benign	0.373	Stabilizing	0.25	N	0.555	neutral	None	None	None	None	N
D/T	0.3233	likely_benign	0.4056	ambiguous	0.485	Stabilizing	0.539	D	0.707	prob.neutral	None	None	None	None	N
D/V	0.2696	likely_benign	0.3407	ambiguous	0.092	Stabilizing	0.781	D	0.821	deleterious	N	0.497002743	None	None	N
D/W	0.877	likely_pathogenic	0.9128	pathogenic	-0.533	Destabilizing	0.982	D	0.785	deleterious	None	None	None	None	N
D/Y	0.2621	likely_benign	0.3418	ambiguous	-0.312	Destabilizing	0.976	D	0.841	deleterious	D	0.53171275	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.