TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7687	23284;23285;23286	chr2:178720960;178720959;178720958	chr2:179585687;179585686;179585685
N2AB	7370	22333;22334;22335	chr2:178720960;178720959;178720958	chr2:179585687;179585686;179585685
N2A	6443	19552;19553;19554	chr2:178720960;178720959;178720958	chr2:179585687;179585686;179585685
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-61
• Domain position: 80
• Structural Position: 163
• Q(SASA): 0.6051
• 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
V/I	None	None	0.78	N	0.382	0.22	0.562540394707	gnomAD-4.0.0	1.62139E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.44818E-05	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	0.0874	likely_benign	0.1178	benign	-0.379	Destabilizing	0.004	N	0.257	neutral	N	0.392163435	None	None	I
V/C	0.7218	likely_pathogenic	0.8071	pathogenic	-0.867	Destabilizing	0.997	D	0.505	neutral	None	None	None	None	I
V/D	0.4713	ambiguous	0.5981	pathogenic	-0.289	Destabilizing	0.984	D	0.612	neutral	N	0.506460519	None	None	I
V/E	0.4129	ambiguous	0.5167	ambiguous	-0.403	Destabilizing	0.976	D	0.529	neutral	None	None	None	None	I
V/F	0.1251	likely_benign	0.178	benign	-0.758	Destabilizing	0.984	D	0.485	neutral	N	0.488807335	None	None	I
V/G	0.2496	likely_benign	0.318	benign	-0.421	Destabilizing	0.811	D	0.518	neutral	D	0.525960213	None	None	I
V/H	0.633	likely_pathogenic	0.7646	pathogenic	-0.025	Destabilizing	0.999	D	0.636	neutral	None	None	None	None	I
V/I	0.0805	likely_benign	0.0922	benign	-0.403	Destabilizing	0.78	D	0.382	neutral	N	0.497061459	None	None	I
V/K	0.6276	likely_pathogenic	0.7494	pathogenic	-0.383	Destabilizing	0.976	D	0.538	neutral	None	None	None	None	I
V/L	0.2257	likely_benign	0.3225	benign	-0.403	Destabilizing	0.78	D	0.391	neutral	N	0.475454035	None	None	I
V/M	0.1458	likely_benign	0.194	benign	-0.62	Destabilizing	0.996	D	0.425	neutral	None	None	None	None	I
V/N	0.3617	ambiguous	0.4698	ambiguous	-0.205	Destabilizing	0.988	D	0.627	neutral	None	None	None	None	I
V/P	0.7586	likely_pathogenic	0.8551	pathogenic	-0.369	Destabilizing	0.988	D	0.581	neutral	None	None	None	None	I
V/Q	0.4838	ambiguous	0.5966	pathogenic	-0.402	Destabilizing	0.988	D	0.608	neutral	None	None	None	None	I
V/R	0.5303	ambiguous	0.6649	pathogenic	0.041	Stabilizing	0.988	D	0.621	neutral	None	None	None	None	I
V/S	0.1709	likely_benign	0.2301	benign	-0.532	Destabilizing	0.851	D	0.513	neutral	None	None	None	None	I
V/T	0.1624	likely_benign	0.2143	benign	-0.557	Destabilizing	0.919	D	0.348	neutral	None	None	None	None	I
V/W	0.7635	likely_pathogenic	0.8787	pathogenic	-0.795	Destabilizing	0.999	D	0.675	prob.neutral	None	None	None	None	I
V/Y	0.5021	ambiguous	0.6572	pathogenic	-0.54	Destabilizing	0.996	D	0.479	neutral	None	None	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.