TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30219	90880;90881;90882	chr2:178552245;178552244;178552243	chr2:179416972;179416971;179416970
N2AB	28578	85957;85958;85959	chr2:178552245;178552244;178552243	chr2:179416972;179416971;179416970
N2A	27651	83176;83177;83178	chr2:178552245;178552244;178552243	chr2:179416972;179416971;179416970
N2B	21154	63685;63686;63687	chr2:178552245;178552244;178552243	chr2:179416972;179416971;179416970
Novex-1	21279	64060;64061;64062	chr2:178552245;178552244;178552243	chr2:179416972;179416971;179416970
Novex-2	21346	64261;64262;64263	chr2:178552245;178552244;178552243	chr2:179416972;179416971;179416970
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-148
• Domain position: 88
• Structural Position: 177
• Q(SASA): 0.3498
• 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
V/F	None	None	0.449	N	0.689	0.278	0.299086750705	gnomAD-4.0.0	1.36876E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.31444E-05
V/I	None	None	0.001	N	0.259	0.085	0.173771789658	gnomAD-4.0.0	6.84382E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	1.73551E-04	0	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
V/A	0.8424	likely_pathogenic	0.7859	pathogenic	-1.824	Destabilizing	0.189	N	0.497	neutral	N	0.482957991	None	None	N
V/C	0.9426	likely_pathogenic	0.9223	pathogenic	-1.543	Destabilizing	0.962	D	0.685	prob.neutral	None	None	None	None	N
V/D	0.9949	likely_pathogenic	0.9909	pathogenic	-1.65	Destabilizing	0.623	D	0.739	prob.delet.	N	0.494821275	None	None	N
V/E	0.9868	likely_pathogenic	0.9773	pathogenic	-1.494	Destabilizing	0.687	D	0.671	neutral	None	None	None	None	N
V/F	0.4067	ambiguous	0.341	ambiguous	-1.117	Destabilizing	0.449	N	0.689	prob.neutral	N	0.493553828	None	None	N
V/G	0.9389	likely_pathogenic	0.9043	pathogenic	-2.318	Highly Destabilizing	0.623	D	0.718	prob.delet.	N	0.494821275	None	None	N
V/H	0.9918	likely_pathogenic	0.9858	pathogenic	-1.911	Destabilizing	0.962	D	0.761	deleterious	None	None	None	None	N
V/I	0.0707	likely_benign	0.0671	benign	-0.494	Destabilizing	0.001	N	0.259	neutral	N	0.489515758	None	None	N
V/K	0.9894	likely_pathogenic	0.9807	pathogenic	-1.513	Destabilizing	0.687	D	0.67	neutral	None	None	None	None	N
V/L	0.2494	likely_benign	0.2176	benign	-0.494	Destabilizing	0.016	N	0.396	neutral	N	0.43685663	None	None	N
V/M	0.3306	likely_benign	0.2801	benign	-0.556	Destabilizing	0.519	D	0.675	prob.neutral	None	None	None	None	N
V/N	0.9789	likely_pathogenic	0.9613	pathogenic	-1.64	Destabilizing	0.87	D	0.748	deleterious	None	None	None	None	N
V/P	0.9872	likely_pathogenic	0.9792	pathogenic	-0.905	Destabilizing	0.87	D	0.695	prob.neutral	None	None	None	None	N
V/Q	0.9848	likely_pathogenic	0.9734	pathogenic	-1.554	Destabilizing	0.87	D	0.7	prob.neutral	None	None	None	None	N
V/R	0.9826	likely_pathogenic	0.9691	pathogenic	-1.277	Destabilizing	0.687	D	0.749	deleterious	None	None	None	None	N
V/S	0.9558	likely_pathogenic	0.9285	pathogenic	-2.362	Highly Destabilizing	0.687	D	0.675	prob.neutral	None	None	None	None	N
V/T	0.8957	likely_pathogenic	0.8496	pathogenic	-2.053	Highly Destabilizing	0.236	N	0.591	neutral	None	None	None	None	N
V/W	0.9842	likely_pathogenic	0.9742	pathogenic	-1.467	Destabilizing	0.962	D	0.743	deleterious	None	None	None	None	N
V/Y	0.9427	likely_pathogenic	0.9032	pathogenic	-1.105	Destabilizing	0.687	D	0.7	prob.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.