TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15909	47950;47951;47952	chr2:178617360;178617359;178617358	chr2:179482087;179482086;179482085
N2AB	14268	43027;43028;43029	chr2:178617360;178617359;178617358	chr2:179482087;179482086;179482085
N2A	13341	40246;40247;40248	chr2:178617360;178617359;178617358	chr2:179482087;179482086;179482085
N2B	6844	20755;20756;20757	chr2:178617360;178617359;178617358	chr2:179482087;179482086;179482085
Novex-1	6969	21130;21131;21132	chr2:178617360;178617359;178617358	chr2:179482087;179482086;179482085
Novex-2	7036	21331;21332;21333	chr2:178617360;178617359;178617358	chr2:179482087;179482086;179482085
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Fn3-3
• Domain position: 51
• Structural Position: 68
• Q(SASA): 0.1078
• 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
C/Y	None	None	1.0	N	0.809	0.428	0.587448292116	gnomAD-4.0.0	6.99096E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.08955E-07	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
C/A	0.7028	likely_pathogenic	0.7658	pathogenic	-1.81	Destabilizing	0.998	D	0.549	neutral	None	None	None	None	I
C/D	0.9595	likely_pathogenic	0.9694	pathogenic	-0.625	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	I
C/E	0.9684	likely_pathogenic	0.9754	pathogenic	-0.472	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	I
C/F	0.7066	likely_pathogenic	0.7493	pathogenic	-1.103	Destabilizing	1.0	D	0.808	deleterious	D	0.524268302	None	None	I
C/G	0.5836	likely_pathogenic	0.6193	pathogenic	-2.15	Highly Destabilizing	1.0	D	0.759	deleterious	D	0.529098451	None	None	I
C/H	0.9228	likely_pathogenic	0.936	pathogenic	-2.078	Highly Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	I
C/I	0.7163	likely_pathogenic	0.7583	pathogenic	-0.916	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
C/K	0.9839	likely_pathogenic	0.9863	pathogenic	-1.103	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	I
C/L	0.7471	likely_pathogenic	0.789	pathogenic	-0.916	Destabilizing	0.999	D	0.55	neutral	None	None	None	None	I
C/M	0.8571	likely_pathogenic	0.8815	pathogenic	0.17	Stabilizing	1.0	D	0.802	deleterious	None	None	None	None	I
C/N	0.8847	likely_pathogenic	0.9065	pathogenic	-1.345	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
C/P	0.988	likely_pathogenic	0.9887	pathogenic	-1.189	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	I
C/Q	0.9369	likely_pathogenic	0.9472	pathogenic	-1.1	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	I
C/R	0.9256	likely_pathogenic	0.9274	pathogenic	-1.076	Destabilizing	1.0	D	0.812	deleterious	D	0.637272423	None	None	I
C/S	0.6444	likely_pathogenic	0.6943	pathogenic	-1.847	Destabilizing	1.0	D	0.719	prob.delet.	N	0.439775885	None	None	I
C/T	0.7327	likely_pathogenic	0.7968	pathogenic	-1.499	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
C/V	0.5753	likely_pathogenic	0.6194	pathogenic	-1.189	Destabilizing	0.999	D	0.635	neutral	None	None	None	None	I
C/W	0.9055	likely_pathogenic	0.9119	pathogenic	-1.178	Destabilizing	1.0	D	0.792	deleterious	D	0.641284247	None	None	I
C/Y	0.8178	likely_pathogenic	0.8406	pathogenic	-1.144	Destabilizing	1.0	D	0.809	deleterious	N	0.477717474	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.