TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2214	6865;6866;6867	chr2:178775071;178775070;178775069	chr2:179639798;179639797;179639796
N2AB	2214	6865;6866;6867	chr2:178775071;178775070;178775069	chr2:179639798;179639797;179639796
N2A	2214	6865;6866;6867	chr2:178775071;178775070;178775069	chr2:179639798;179639797;179639796
N2B	2168	6727;6728;6729	chr2:178775071;178775070;178775069	chr2:179639798;179639797;179639796
Novex-1	2168	6727;6728;6729	chr2:178775071;178775070;178775069	chr2:179639798;179639797;179639796
Novex-2	2168	6727;6728;6729	chr2:178775071;178775070;178775069	chr2:179639798;179639797;179639796
Novex-3	2214	6865;6866;6867	chr2:178775071;178775070;178775069	chr2:179639798;179639797;179639796

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-11
• Domain position: 41
• Structural Position: 58
• Q(SASA): 0.1733
• 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	rs2092054706	None	None	N	0.145	0.177	0.137902524267	gnomAD-4.0.0	1.59077E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85678E-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	0.4642	ambiguous	0.4501	ambiguous	-2.028	Highly Destabilizing	0.052	N	0.565	neutral	N	0.506729759	None	None	N
V/C	0.7715	likely_pathogenic	0.7566	pathogenic	-1.182	Destabilizing	0.935	D	0.619	neutral	None	None	None	None	N
V/D	0.9048	likely_pathogenic	0.8995	pathogenic	-2.742	Highly Destabilizing	0.484	N	0.687	prob.neutral	D	0.542648222	None	None	N
V/E	0.8207	likely_pathogenic	0.8119	pathogenic	-2.529	Highly Destabilizing	0.555	D	0.647	neutral	None	None	None	None	N
V/F	0.2332	likely_benign	0.231	benign	-1.352	Destabilizing	0.317	N	0.664	neutral	N	0.515941783	None	None	N
V/G	0.5744	likely_pathogenic	0.5586	ambiguous	-2.508	Highly Destabilizing	0.484	N	0.681	prob.neutral	D	0.541766344	None	None	N
V/H	0.8975	likely_pathogenic	0.8904	pathogenic	-2.212	Highly Destabilizing	0.935	D	0.639	neutral	None	None	None	None	N
V/I	0.0527	likely_benign	0.0528	benign	-0.678	Destabilizing	None	N	0.145	neutral	N	0.336228558	None	None	N
V/K	0.8229	likely_pathogenic	0.8137	pathogenic	-1.644	Destabilizing	0.555	D	0.65	neutral	None	None	None	None	N
V/L	0.1131	likely_benign	0.1075	benign	-0.678	Destabilizing	None	N	0.181	neutral	N	0.36781175	None	None	N
V/M	0.1602	likely_benign	0.1562	benign	-0.502	Destabilizing	0.38	N	0.648	neutral	None	None	None	None	N
V/N	0.7438	likely_pathogenic	0.7366	pathogenic	-1.92	Destabilizing	0.791	D	0.695	prob.neutral	None	None	None	None	N
V/P	0.8653	likely_pathogenic	0.8575	pathogenic	-1.105	Destabilizing	0.791	D	0.669	neutral	None	None	None	None	N
V/Q	0.8071	likely_pathogenic	0.7959	pathogenic	-1.819	Destabilizing	0.791	D	0.635	neutral	None	None	None	None	N
V/R	0.7565	likely_pathogenic	0.7481	pathogenic	-1.454	Destabilizing	0.555	D	0.696	prob.neutral	None	None	None	None	N
V/S	0.6626	likely_pathogenic	0.6458	pathogenic	-2.444	Highly Destabilizing	0.262	N	0.629	neutral	None	None	None	None	N
V/T	0.5444	ambiguous	0.5284	ambiguous	-2.104	Highly Destabilizing	0.149	N	0.575	neutral	None	None	None	None	N
V/W	0.8733	likely_pathogenic	0.8723	pathogenic	-1.862	Destabilizing	0.935	D	0.666	neutral	None	None	None	None	N
V/Y	0.7048	likely_pathogenic	0.6993	pathogenic	-1.446	Destabilizing	0.555	D	0.674	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.