TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24177	72754;72755;72756	chr2:178573603;178573602;178573601	chr2:179438330;179438329;179438328
N2AB	22536	67831;67832;67833	chr2:178573603;178573602;178573601	chr2:179438330;179438329;179438328
N2A	21609	65050;65051;65052	chr2:178573603;178573602;178573601	chr2:179438330;179438329;179438328
N2B	15112	45559;45560;45561	chr2:178573603;178573602;178573601	chr2:179438330;179438329;179438328
Novex-1	15237	45934;45935;45936	chr2:178573603;178573602;178573601	chr2:179438330;179438329;179438328
Novex-2	15304	46135;46136;46137	chr2:178573603;178573602;178573601	chr2:179438330;179438329;179438328
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-63
• Domain position: 56
• Structural Position: 77
• Q(SASA): 0.1328
• 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	rs1031881489	None	0.201	N	0.537	0.096	0.321672782286	gnomAD-4.0.0	7.43576E-07	None	None	None	None	N	None	3.35053E-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
V/A	0.2907	likely_benign	0.3211	benign	-1.771	Destabilizing	0.002	N	0.22	neutral	N	0.494812508	None	None	N
V/C	0.7202	likely_pathogenic	0.7407	pathogenic	-1.239	Destabilizing	0.977	D	0.542	neutral	None	None	None	None	N
V/D	0.8137	likely_pathogenic	0.8369	pathogenic	-2.092	Highly Destabilizing	0.81	D	0.635	neutral	N	0.479545085	None	None	N
V/E	0.6672	likely_pathogenic	0.6991	pathogenic	-1.9	Destabilizing	0.617	D	0.611	neutral	None	None	None	None	N
V/F	0.389	ambiguous	0.4022	ambiguous	-0.985	Destabilizing	0.81	D	0.603	neutral	N	0.479420181	None	None	N
V/G	0.4071	ambiguous	0.4256	ambiguous	-2.285	Highly Destabilizing	0.379	N	0.609	neutral	N	0.514782349	None	None	N
V/H	0.8772	likely_pathogenic	0.8901	pathogenic	-2.004	Highly Destabilizing	0.992	D	0.594	neutral	None	None	None	None	N
V/I	0.0831	likely_benign	0.0909	benign	-0.36	Destabilizing	0.201	N	0.537	neutral	N	0.454699469	None	None	N
V/K	0.8097	likely_pathogenic	0.8245	pathogenic	-1.508	Destabilizing	0.617	D	0.621	neutral	None	None	None	None	N
V/L	0.2491	likely_benign	0.2862	benign	-0.36	Destabilizing	0.002	N	0.184	neutral	N	0.468204697	None	None	N
V/M	0.205	likely_benign	0.2411	benign	-0.371	Destabilizing	0.85	D	0.624	neutral	None	None	None	None	N
V/N	0.5802	likely_pathogenic	0.6245	pathogenic	-1.724	Destabilizing	0.85	D	0.625	neutral	None	None	None	None	N
V/P	0.8264	likely_pathogenic	0.8427	pathogenic	-0.8	Destabilizing	0.92	D	0.608	neutral	None	None	None	None	N
V/Q	0.6769	likely_pathogenic	0.7121	pathogenic	-1.599	Destabilizing	0.85	D	0.623	neutral	None	None	None	None	N
V/R	0.7953	likely_pathogenic	0.8063	pathogenic	-1.319	Destabilizing	0.85	D	0.631	neutral	None	None	None	None	N
V/S	0.4303	ambiguous	0.4782	ambiguous	-2.351	Highly Destabilizing	0.021	N	0.541	neutral	None	None	None	None	N
V/T	0.3465	ambiguous	0.3916	ambiguous	-2.018	Highly Destabilizing	0.447	N	0.568	neutral	None	None	None	None	N
V/W	0.9538	likely_pathogenic	0.9558	pathogenic	-1.48	Destabilizing	0.992	D	0.626	neutral	None	None	None	None	N
V/Y	0.7985	likely_pathogenic	0.8158	pathogenic	-1.064	Destabilizing	0.972	D	0.611	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.