TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18646	56161;56162;56163	chr2:178600968;178600967;178600966	chr2:179465695;179465694;179465693
N2AB	17005	51238;51239;51240	chr2:178600968;178600967;178600966	chr2:179465695;179465694;179465693
N2A	16078	48457;48458;48459	chr2:178600968;178600967;178600966	chr2:179465695;179465694;179465693
N2B	9581	28966;28967;28968	chr2:178600968;178600967;178600966	chr2:179465695;179465694;179465693
Novex-1	9706	29341;29342;29343	chr2:178600968;178600967;178600966	chr2:179465695;179465694;179465693
Novex-2	9773	29542;29543;29544	chr2:178600968;178600967;178600966	chr2:179465695;179465694;179465693
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: Fn3-23
• Domain position: 68
• Structural Position: 93
• Q(SASA): 0.0947
• 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/A	rs2053262199	None	0.014	N	0.383	0.231	0.47185959272	gnomAD-4.0.0	3.4224E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49888E-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	0.3013	likely_benign	0.2405	benign	-1.781	Destabilizing	0.014	N	0.383	neutral	N	0.477176271	None	None	N
V/C	0.8718	likely_pathogenic	0.8649	pathogenic	-1.348	Destabilizing	0.994	D	0.725	prob.delet.	None	None	None	None	N
V/D	0.9802	likely_pathogenic	0.977	pathogenic	-2.248	Highly Destabilizing	0.971	D	0.837	deleterious	N	0.494457606	None	None	N
V/E	0.9453	likely_pathogenic	0.9368	pathogenic	-1.999	Destabilizing	0.956	D	0.804	deleterious	None	None	None	None	N
V/F	0.7316	likely_pathogenic	0.7015	pathogenic	-1.021	Destabilizing	0.971	D	0.725	prob.delet.	N	0.499809522	None	None	N
V/G	0.7698	likely_pathogenic	0.7462	pathogenic	-2.351	Highly Destabilizing	0.89	D	0.795	deleterious	N	0.52171612	None	None	N
V/H	0.9833	likely_pathogenic	0.98	pathogenic	-2.155	Highly Destabilizing	0.998	D	0.82	deleterious	None	None	None	None	N
V/I	0.1084	likely_benign	0.0975	benign	-0.184	Destabilizing	0.058	N	0.286	neutral	N	0.47444281	None	None	N
V/K	0.9469	likely_pathogenic	0.9463	pathogenic	-1.43	Destabilizing	0.956	D	0.806	deleterious	None	None	None	None	N
V/L	0.5288	ambiguous	0.5079	ambiguous	-0.184	Destabilizing	0.489	N	0.617	neutral	N	0.510840753	None	None	N
V/M	0.4218	ambiguous	0.3754	ambiguous	-0.294	Destabilizing	0.978	D	0.695	prob.neutral	None	None	None	None	N
V/N	0.9518	likely_pathogenic	0.9376	pathogenic	-1.817	Destabilizing	0.978	D	0.835	deleterious	None	None	None	None	N
V/P	0.9504	likely_pathogenic	0.9427	pathogenic	-0.688	Destabilizing	0.978	D	0.806	deleterious	None	None	None	None	N
V/Q	0.9349	likely_pathogenic	0.9232	pathogenic	-1.589	Destabilizing	0.978	D	0.819	deleterious	None	None	None	None	N
V/R	0.9194	likely_pathogenic	0.9194	pathogenic	-1.435	Destabilizing	0.956	D	0.83	deleterious	None	None	None	None	N
V/S	0.7593	likely_pathogenic	0.7059	pathogenic	-2.463	Highly Destabilizing	0.915	D	0.78	deleterious	None	None	None	None	N
V/T	0.5125	ambiguous	0.4554	ambiguous	-2.048	Highly Destabilizing	0.86	D	0.654	neutral	None	None	None	None	N
V/W	0.9915	likely_pathogenic	0.9899	pathogenic	-1.537	Destabilizing	0.998	D	0.781	deleterious	None	None	None	None	N
V/Y	0.9645	likely_pathogenic	0.961	pathogenic	-1.088	Destabilizing	0.993	D	0.714	prob.delet.	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.