TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25257	75994;75995;75996	chr2:178570363;178570362;178570361	chr2:179435090;179435089;179435088
N2AB	23616	71071;71072;71073	chr2:178570363;178570362;178570361	chr2:179435090;179435089;179435088
N2A	22689	68290;68291;68292	chr2:178570363;178570362;178570361	chr2:179435090;179435089;179435088
N2B	16192	48799;48800;48801	chr2:178570363;178570362;178570361	chr2:179435090;179435089;179435088
Novex-1	16317	49174;49175;49176	chr2:178570363;178570362;178570361	chr2:179435090;179435089;179435088
Novex-2	16384	49375;49376;49377	chr2:178570363;178570362;178570361	chr2:179435090;179435089;179435088
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Fn3-71
• Domain position: 54
• Structural Position: 70
• Q(SASA): 0.3971
• 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
A/G	None	None	0.042	N	0.28	0.102	0.224531998449	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
A/C	0.3055	likely_benign	0.3767	ambiguous	-0.849	Destabilizing	0.667	D	0.363	neutral	None	None	None	None	N
A/D	0.2529	likely_benign	0.2782	benign	-1.047	Destabilizing	0.175	N	0.368	neutral	N	0.434364269	None	None	N
A/E	0.2394	likely_benign	0.2555	benign	-1.163	Destabilizing	0.055	N	0.349	neutral	None	None	None	None	N
A/F	0.345	ambiguous	0.3834	ambiguous	-1.148	Destabilizing	0.497	N	0.381	neutral	None	None	None	None	N
A/G	0.0964	likely_benign	0.1026	benign	-0.879	Destabilizing	0.042	N	0.28	neutral	N	0.415394506	None	None	N
A/H	0.4032	ambiguous	0.4341	ambiguous	-0.946	Destabilizing	0.667	D	0.337	neutral	None	None	None	None	N
A/I	0.2152	likely_benign	0.2413	benign	-0.522	Destabilizing	0.046	N	0.347	neutral	None	None	None	None	N
A/K	0.3603	ambiguous	0.4039	ambiguous	-1.082	Destabilizing	0.124	N	0.358	neutral	None	None	None	None	N
A/L	0.1555	likely_benign	0.1743	benign	-0.522	Destabilizing	None	N	0.177	neutral	None	None	None	None	N
A/M	0.1887	likely_benign	0.2108	benign	-0.335	Destabilizing	0.497	N	0.343	neutral	None	None	None	None	N
A/N	0.1625	likely_benign	0.1788	benign	-0.734	Destabilizing	0.124	N	0.408	neutral	None	None	None	None	N
A/P	0.1426	likely_benign	0.1484	benign	-0.554	Destabilizing	0.001	N	0.204	neutral	N	0.42849709	None	None	N
A/Q	0.2822	likely_benign	0.3024	benign	-1.024	Destabilizing	0.011	N	0.207	neutral	None	None	None	None	N
A/R	0.3624	ambiguous	0.4021	ambiguous	-0.563	Destabilizing	0.22	N	0.375	neutral	None	None	None	None	N
A/S	0.0743	likely_benign	0.0772	benign	-0.986	Destabilizing	None	N	0.065	neutral	N	0.38713047	None	None	N
A/T	0.0716	likely_benign	0.0741	benign	-1.025	Destabilizing	0.042	N	0.254	neutral	N	0.430515887	None	None	N
A/V	0.1191	likely_benign	0.1289	benign	-0.554	Destabilizing	0.001	N	0.105	neutral	N	0.469105987	None	None	N
A/W	0.6851	likely_pathogenic	0.7244	pathogenic	-1.345	Destabilizing	0.958	D	0.428	neutral	None	None	None	None	N
A/Y	0.393	ambiguous	0.4368	ambiguous	-0.999	Destabilizing	0.667	D	0.37	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.