TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32884	98875;98876;98877	chr2:178539415;178539414;178539413	chr2:179404142;179404141;179404140
N2AB	31243	93952;93953;93954	chr2:178539415;178539414;178539413	chr2:179404142;179404141;179404140
N2A	30316	91171;91172;91173	chr2:178539415;178539414;178539413	chr2:179404142;179404141;179404140
N2B	23819	71680;71681;71682	chr2:178539415;178539414;178539413	chr2:179404142;179404141;179404140
Novex-1	23944	72055;72056;72057	chr2:178539415;178539414;178539413	chr2:179404142;179404141;179404140
Novex-2	24011	72256;72257;72258	chr2:178539415;178539414;178539413	chr2:179404142;179404141;179404140
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Fn3-127
• Domain position: 90
• Structural Position: 123
• Q(SASA): 0.1511
• 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
S/Y	None	None	0.999	N	0.879	0.455	0.659942566833	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	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
S/A	0.1794	likely_benign	0.1589	benign	-0.547	Destabilizing	0.994	D	0.608	neutral	N	0.479950204	None	None	N
S/C	0.2894	likely_benign	0.2557	benign	-0.294	Destabilizing	1.0	D	0.81	deleterious	N	0.519339945	None	None	N
S/D	0.8814	likely_pathogenic	0.8747	pathogenic	-0.817	Destabilizing	0.998	D	0.665	prob.neutral	None	None	None	None	N
S/E	0.9471	likely_pathogenic	0.9429	pathogenic	-0.681	Destabilizing	0.998	D	0.682	prob.neutral	None	None	None	None	N
S/F	0.8945	likely_pathogenic	0.8664	pathogenic	-0.27	Destabilizing	0.999	D	0.87	deleterious	N	0.497641292	None	None	N
S/G	0.226	likely_benign	0.1967	benign	-0.928	Destabilizing	0.998	D	0.691	prob.delet.	None	None	None	None	N
S/H	0.9176	likely_pathogenic	0.908	pathogenic	-1.368	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
S/I	0.7467	likely_pathogenic	0.701	pathogenic	0.402	Stabilizing	0.999	D	0.833	deleterious	None	None	None	None	N
S/K	0.9889	likely_pathogenic	0.9871	pathogenic	-0.594	Destabilizing	0.998	D	0.67	prob.neutral	None	None	None	None	N
S/L	0.5081	ambiguous	0.4535	ambiguous	0.402	Stabilizing	0.999	D	0.801	deleterious	None	None	None	None	N
S/M	0.6152	likely_pathogenic	0.588	pathogenic	0.387	Stabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
S/N	0.6452	likely_pathogenic	0.6125	pathogenic	-0.952	Destabilizing	0.998	D	0.695	prob.delet.	None	None	None	None	N
S/P	0.9254	likely_pathogenic	0.8948	pathogenic	0.122	Stabilizing	0.999	D	0.823	deleterious	N	0.49020727	None	None	N
S/Q	0.947	likely_pathogenic	0.9403	pathogenic	-0.75	Destabilizing	0.999	D	0.818	deleterious	None	None	None	None	N
S/R	0.9862	likely_pathogenic	0.983	pathogenic	-0.881	Destabilizing	0.999	D	0.823	deleterious	None	None	None	None	N
S/T	0.187	likely_benign	0.1872	benign	-0.708	Destabilizing	0.997	D	0.651	prob.neutral	N	0.438180939	None	None	N
S/V	0.6648	likely_pathogenic	0.6203	pathogenic	0.122	Stabilizing	0.999	D	0.838	deleterious	None	None	None	None	N
S/W	0.9021	likely_pathogenic	0.8814	pathogenic	-0.532	Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
S/Y	0.8274	likely_pathogenic	0.786	pathogenic	-0.14	Destabilizing	0.999	D	0.879	deleterious	N	0.519846924	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.