TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8796	26611;26612;26613	chr2:178714388;178714387;178714386	chr2:179579115;179579114;179579113
N2AB	8479	25660;25661;25662	chr2:178714388;178714387;178714386	chr2:179579115;179579114;179579113
N2A	7552	22879;22880;22881	chr2:178714388;178714387;178714386	chr2:179579115;179579114;179579113
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: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-73
• Domain position: 61
• Structural Position: 140
• Q(SASA): 0.1576
• 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
F/C	None	None	0.929	N	0.787	0.554	0.71030341735	gnomAD-4.0.0	3.42113E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49748E-06	0	0
F/L	rs1193918191	-0.784	None	N	0.3	0.135	0.213573922156	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
F/L	rs1193918191	-0.784	None	N	0.3	0.135	0.213573922156	gnomAD-4.0.0	1.59133E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8585E-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
F/A	0.665	likely_pathogenic	0.7094	pathogenic	-3.292	Highly Destabilizing	0.067	N	0.619	neutral	None	None	None	None	N
F/C	0.2614	likely_benign	0.3395	benign	-2.459	Highly Destabilizing	0.929	D	0.787	deleterious	N	0.503747813	None	None	N
F/D	0.9259	likely_pathogenic	0.9355	pathogenic	-3.971	Highly Destabilizing	0.993	D	0.777	deleterious	None	None	None	None	N
F/E	0.9223	likely_pathogenic	0.9304	pathogenic	-3.742	Highly Destabilizing	0.937	D	0.75	deleterious	None	None	None	None	N
F/G	0.8364	likely_pathogenic	0.8569	pathogenic	-3.766	Highly Destabilizing	0.98	D	0.734	prob.delet.	None	None	None	None	N
F/H	0.7746	likely_pathogenic	0.7817	pathogenic	-2.424	Highly Destabilizing	0.838	D	0.737	prob.delet.	None	None	None	None	N
F/I	0.0893	likely_benign	0.0924	benign	-1.723	Destabilizing	None	N	0.297	neutral	N	0.351758741	None	None	N
F/K	0.9246	likely_pathogenic	0.9268	pathogenic	-2.661	Highly Destabilizing	0.954	D	0.747	deleterious	None	None	None	None	N
F/L	0.4696	ambiguous	0.4433	ambiguous	-1.723	Destabilizing	None	N	0.3	neutral	N	0.41290128	None	None	N
F/M	0.2996	likely_benign	0.2909	benign	-1.571	Destabilizing	0.098	N	0.609	neutral	None	None	None	None	N
F/N	0.799	likely_pathogenic	0.8233	pathogenic	-3.249	Highly Destabilizing	0.998	D	0.805	deleterious	None	None	None	None	N
F/P	0.9762	likely_pathogenic	0.9761	pathogenic	-2.263	Highly Destabilizing	0.998	D	0.809	deleterious	None	None	None	None	N
F/Q	0.8766	likely_pathogenic	0.8753	pathogenic	-3.162	Highly Destabilizing	0.994	D	0.817	deleterious	None	None	None	None	N
F/R	0.8762	likely_pathogenic	0.878	pathogenic	-2.156	Highly Destabilizing	0.986	D	0.807	deleterious	None	None	None	None	N
F/S	0.6649	likely_pathogenic	0.7361	pathogenic	-3.849	Highly Destabilizing	0.974	D	0.695	prob.neutral	N	0.503494323	None	None	N
F/T	0.6959	likely_pathogenic	0.7395	pathogenic	-3.497	Highly Destabilizing	0.91	D	0.679	prob.neutral	None	None	None	None	N
F/V	0.1347	likely_benign	0.1529	benign	-2.263	Highly Destabilizing	None	N	0.435	neutral	N	0.441973393	None	None	N
F/W	0.506	ambiguous	0.5063	ambiguous	-0.749	Destabilizing	0.973	D	0.584	neutral	None	None	None	None	N
F/Y	0.2094	likely_benign	0.2345	benign	-1.229	Destabilizing	0.184	N	0.504	neutral	N	0.503747813	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.