TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2454	7585;7586;7587	chr2:178773696;178773695;178773694	chr2:179638423;179638422;179638421
N2AB	2454	7585;7586;7587	chr2:178773696;178773695;178773694	chr2:179638423;179638422;179638421
N2A	2454	7585;7586;7587	chr2:178773696;178773695;178773694	chr2:179638423;179638422;179638421
N2B	2408	7447;7448;7449	chr2:178773696;178773695;178773694	chr2:179638423;179638422;179638421
Novex-1	2408	7447;7448;7449	chr2:178773696;178773695;178773694	chr2:179638423;179638422;179638421
Novex-2	2408	7447;7448;7449	chr2:178773696;178773695;178773694	chr2:179638423;179638422;179638421
Novex-3	2454	7585;7586;7587	chr2:178773696;178773695;178773694	chr2:179638423;179638422;179638421

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-14
• Domain position: 10
• Structural Position: 13
• Q(SASA): 0.3089
• 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/D	rs2091855424	None	0.81	D	0.559	0.752	0.86537904985	gnomAD-4.0.0	1.59073E-06	None	None	None	None	N	None	5.65291E-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	0.1944	likely_benign	0.1929	benign	-1.204	Destabilizing	0.334	N	0.415	neutral	N	0.514408311	None	None	N
V/C	0.6567	likely_pathogenic	0.6511	pathogenic	-0.847	Destabilizing	0.992	D	0.445	neutral	None	None	None	None	N
V/D	0.3971	ambiguous	0.3911	ambiguous	-0.918	Destabilizing	0.81	D	0.559	neutral	D	0.70273508	None	None	N
V/E	0.3128	likely_benign	0.3068	benign	-0.976	Destabilizing	0.739	D	0.472	neutral	None	None	None	None	N
V/F	0.1728	likely_benign	0.1724	benign	-1.179	Destabilizing	0.81	D	0.431	neutral	D	0.701238865	None	None	N
V/G	0.2686	likely_benign	0.2635	benign	-1.456	Destabilizing	0.896	D	0.519	neutral	D	0.70204869	None	None	N
V/H	0.5454	ambiguous	0.5406	ambiguous	-1.066	Destabilizing	0.977	D	0.585	neutral	None	None	None	None	N
V/I	0.0719	likely_benign	0.0704	benign	-0.644	Destabilizing	0.004	N	0.128	neutral	D	0.538856829	None	None	N
V/K	0.3222	likely_benign	0.325	benign	-0.94	Destabilizing	0.739	D	0.468	neutral	None	None	None	None	N
V/L	0.1915	likely_benign	0.1881	benign	-0.644	Destabilizing	0.002	N	0.117	neutral	N	0.505521444	None	None	N
V/M	0.1144	likely_benign	0.11	benign	-0.456	Destabilizing	0.85	D	0.403	neutral	None	None	None	None	N
V/N	0.2575	likely_benign	0.253	benign	-0.641	Destabilizing	0.92	D	0.581	neutral	None	None	None	None	N
V/P	0.9026	likely_pathogenic	0.9065	pathogenic	-0.795	Destabilizing	0.972	D	0.529	neutral	None	None	None	None	N
V/Q	0.2987	likely_benign	0.2923	benign	-0.875	Destabilizing	0.25	N	0.399	neutral	None	None	None	None	N
V/R	0.3018	likely_benign	0.3089	benign	-0.413	Destabilizing	0.85	D	0.571	neutral	None	None	None	None	N
V/S	0.2345	likely_benign	0.2319	benign	-1.111	Destabilizing	0.85	D	0.475	neutral	None	None	None	None	N
V/T	0.16	likely_benign	0.1584	benign	-1.06	Destabilizing	0.617	D	0.38	neutral	None	None	None	None	N
V/W	0.793	likely_pathogenic	0.7939	pathogenic	-1.298	Destabilizing	0.992	D	0.665	neutral	None	None	None	None	N
V/Y	0.5115	ambiguous	0.5149	ambiguous	-1.002	Destabilizing	0.92	D	0.448	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.