TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2210	6853;6854;6855	chr2:178775083;178775082;178775081	chr2:179639810;179639809;179639808
N2AB	2210	6853;6854;6855	chr2:178775083;178775082;178775081	chr2:179639810;179639809;179639808
N2A	2210	6853;6854;6855	chr2:178775083;178775082;178775081	chr2:179639810;179639809;179639808
N2B	2164	6715;6716;6717	chr2:178775083;178775082;178775081	chr2:179639810;179639809;179639808
Novex-1	2164	6715;6716;6717	chr2:178775083;178775082;178775081	chr2:179639810;179639809;179639808
Novex-2	2164	6715;6716;6717	chr2:178775083;178775082;178775081	chr2:179639810;179639809;179639808
Novex-3	2210	6853;6854;6855	chr2:178775083;178775082;178775081	chr2:179639810;179639809;179639808

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-11
• Domain position: 37
• Structural Position: 51
• Q(SASA): 0.6097
• 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
D/N	rs2154345509	None	0.001	N	0.068	0.078	0.0482279557977	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
D/A	0.1036	likely_benign	0.1021	benign	-0.009	Destabilizing	0.334	N	0.353	neutral	N	0.423788125	None	None	N
D/C	0.3556	ambiguous	0.3273	benign	0.191	Stabilizing	0.992	D	0.421	neutral	None	None	None	None	N
D/E	0.1487	likely_benign	0.1445	benign	-0.098	Destabilizing	0.334	N	0.246	neutral	N	0.32635131	None	None	N
D/F	0.4046	ambiguous	0.4012	ambiguous	-0.179	Destabilizing	0.972	D	0.425	neutral	None	None	None	None	N
D/G	0.0757	likely_benign	0.0743	benign	-0.155	Destabilizing	0.002	N	0.103	neutral	N	0.353459998	None	None	N
D/H	0.1584	likely_benign	0.1543	benign	0.064	Stabilizing	0.81	D	0.351	neutral	N	0.425277675	None	None	N
D/I	0.3474	ambiguous	0.3516	ambiguous	0.312	Stabilizing	0.92	D	0.449	neutral	None	None	None	None	N
D/K	0.1949	likely_benign	0.1968	benign	0.415	Stabilizing	0.447	N	0.334	neutral	None	None	None	None	N
D/L	0.2947	likely_benign	0.2914	benign	0.312	Stabilizing	0.766	D	0.427	neutral	None	None	None	None	N
D/M	0.4446	ambiguous	0.4377	ambiguous	0.343	Stabilizing	0.992	D	0.409	neutral	None	None	None	None	N
D/N	0.0526	likely_benign	0.0523	benign	0.39	Stabilizing	0.001	N	0.068	neutral	N	0.339241628	None	None	N
D/P	0.8679	likely_pathogenic	0.8712	pathogenic	0.226	Stabilizing	0.92	D	0.355	neutral	None	None	None	None	N
D/Q	0.2038	likely_benign	0.2006	benign	0.384	Stabilizing	0.85	D	0.299	neutral	None	None	None	None	N
D/R	0.2078	likely_benign	0.2073	benign	0.526	Stabilizing	0.617	D	0.404	neutral	None	None	None	None	N
D/S	0.0811	likely_benign	0.08	benign	0.232	Stabilizing	0.25	N	0.251	neutral	None	None	None	None	N
D/T	0.2138	likely_benign	0.2106	benign	0.336	Stabilizing	0.617	D	0.318	neutral	None	None	None	None	N
D/V	0.2213	likely_benign	0.2237	benign	0.226	Stabilizing	0.896	D	0.425	neutral	N	0.404560236	None	None	N
D/W	0.7256	likely_pathogenic	0.7173	pathogenic	-0.16	Destabilizing	0.992	D	0.497	neutral	None	None	None	None	N
D/Y	0.133	likely_benign	0.1297	benign	0.036	Stabilizing	0.963	D	0.425	neutral	N	0.404560236	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.