TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28722	86389;86390;86391	chr2:178559968;178559967;178559966	chr2:179424695;179424694;179424693
N2AB	27081	81466;81467;81468	chr2:178559968;178559967;178559966	chr2:179424695;179424694;179424693
N2A	26154	78685;78686;78687	chr2:178559968;178559967;178559966	chr2:179424695;179424694;179424693
N2B	19657	59194;59195;59196	chr2:178559968;178559967;178559966	chr2:179424695;179424694;179424693
Novex-1	19782	59569;59570;59571	chr2:178559968;178559967;178559966	chr2:179424695;179424694;179424693
Novex-2	19849	59770;59771;59772	chr2:178559968;178559967;178559966	chr2:179424695;179424694;179424693
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-97
• Domain position: 72
• Structural Position: 105
• Q(SASA): 0.1468
• 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/I	None	None	0.004	N	0.451	0.071	0.162503812791	gnomAD-4.0.0	1.59135E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85817E-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
V/A	0.1503	likely_benign	0.1499	benign	-1.872	Destabilizing	0.004	N	0.379	neutral	N	0.511688902	None	None	N
V/C	0.4742	ambiguous	0.4779	ambiguous	-1.278	Destabilizing	0.977	D	0.658	neutral	None	None	None	None	N
V/D	0.3382	likely_benign	0.3176	benign	-2.385	Highly Destabilizing	0.379	N	0.684	prob.neutral	N	0.501165264	None	None	N
V/E	0.2361	likely_benign	0.2111	benign	-2.138	Highly Destabilizing	0.005	N	0.591	neutral	None	None	None	None	N
V/F	0.1231	likely_benign	0.1322	benign	-1.042	Destabilizing	0.81	D	0.674	neutral	N	0.488852115	None	None	N
V/G	0.2194	likely_benign	0.2151	benign	-2.402	Highly Destabilizing	0.379	N	0.669	neutral	N	0.478472356	None	None	N
V/H	0.3587	ambiguous	0.3551	ambiguous	-2.262	Highly Destabilizing	0.026	N	0.639	neutral	None	None	None	None	N
V/I	0.0672	likely_benign	0.0697	benign	-0.377	Destabilizing	0.004	N	0.451	neutral	N	0.486177169	None	None	N
V/K	0.3041	likely_benign	0.2753	benign	-1.256	Destabilizing	0.447	N	0.643	neutral	None	None	None	None	N
V/L	0.1181	likely_benign	0.1206	benign	-0.377	Destabilizing	0.08	N	0.641	neutral	N	0.456817054	None	None	N
V/M	0.0996	likely_benign	0.1048	benign	-0.601	Destabilizing	0.85	D	0.667	neutral	None	None	None	None	N
V/N	0.1892	likely_benign	0.1902	benign	-1.657	Destabilizing	0.85	D	0.699	prob.neutral	None	None	None	None	N
V/P	0.9248	likely_pathogenic	0.9259	pathogenic	-0.852	Destabilizing	0.92	D	0.659	neutral	None	None	None	None	N
V/Q	0.2267	likely_benign	0.2138	benign	-1.423	Destabilizing	0.739	D	0.661	neutral	None	None	None	None	N
V/R	0.2507	likely_benign	0.2257	benign	-1.308	Destabilizing	0.85	D	0.694	prob.neutral	None	None	None	None	N
V/S	0.1419	likely_benign	0.1416	benign	-2.228	Highly Destabilizing	0.021	N	0.592	neutral	None	None	None	None	N
V/T	0.1251	likely_benign	0.1246	benign	-1.841	Destabilizing	0.447	N	0.643	neutral	None	None	None	None	N
V/W	0.6454	likely_pathogenic	0.6681	pathogenic	-1.571	Destabilizing	0.992	D	0.739	prob.delet.	None	None	None	None	N
V/Y	0.3532	ambiguous	0.3461	ambiguous	-1.17	Destabilizing	0.85	D	0.678	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.