TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2749	8470;8471;8472	chr2:178770547;178770546;178770545	chr2:179635274;179635273;179635272
N2AB	2749	8470;8471;8472	chr2:178770547;178770546;178770545	chr2:179635274;179635273;179635272
N2A	2749	8470;8471;8472	chr2:178770547;178770546;178770545	chr2:179635274;179635273;179635272
N2B	2703	8332;8333;8334	chr2:178770547;178770546;178770545	chr2:179635274;179635273;179635272
Novex-1	2703	8332;8333;8334	chr2:178770547;178770546;178770545	chr2:179635274;179635273;179635272
Novex-2	2703	8332;8333;8334	chr2:178770547;178770546;178770545	chr2:179635274;179635273;179635272
Novex-3	2749	8470;8471;8472	chr2:178770547;178770546;178770545	chr2:179635274;179635273;179635272

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Ig-17
• Domain position: 43
• Structural Position: 70
• Q(SASA): 0.6121
• 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
S/P	None	None	0.003	N	0.249	0.223	0.218112801441	gnomAD-4.0.0	1.59049E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85649E-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
S/A	0.0794	likely_benign	0.0831	benign	-0.295	Destabilizing	0.349	N	0.447	neutral	N	0.510848109	None	None	N
S/C	0.1536	likely_benign	0.1834	benign	-0.272	Destabilizing	0.995	D	0.542	neutral	D	0.597221595	None	None	N
S/D	0.1666	likely_benign	0.1828	benign	0.173	Stabilizing	0.633	D	0.376	neutral	None	None	None	None	N
S/E	0.2679	likely_benign	0.3077	benign	0.076	Stabilizing	0.775	D	0.381	neutral	None	None	None	None	N
S/F	0.2947	likely_benign	0.3416	ambiguous	-0.928	Destabilizing	0.983	D	0.574	neutral	N	0.521446314	None	None	N
S/G	0.0881	likely_benign	0.0824	benign	-0.394	Destabilizing	0.775	D	0.407	neutral	None	None	None	None	N
S/H	0.2735	likely_benign	0.3349	benign	-0.885	Destabilizing	0.989	D	0.508	neutral	None	None	None	None	N
S/I	0.2071	likely_benign	0.2277	benign	-0.169	Destabilizing	0.961	D	0.569	neutral	None	None	None	None	N
S/K	0.3916	ambiguous	0.4781	ambiguous	-0.432	Destabilizing	0.775	D	0.41	neutral	None	None	None	None	N
S/L	0.1273	likely_benign	0.1389	benign	-0.169	Destabilizing	0.775	D	0.499	neutral	None	None	None	None	N
S/M	0.2262	likely_benign	0.2412	benign	0.015	Stabilizing	0.996	D	0.523	neutral	None	None	None	None	N
S/N	0.0835	likely_benign	0.0778	benign	-0.17	Destabilizing	0.044	N	0.231	neutral	None	None	None	None	N
S/P	0.0749	likely_benign	0.0822	benign	-0.182	Destabilizing	0.003	N	0.249	neutral	N	0.444106878	None	None	N
S/Q	0.3266	likely_benign	0.3921	ambiguous	-0.406	Destabilizing	0.961	D	0.438	neutral	None	None	None	None	N
S/R	0.3741	ambiguous	0.4421	ambiguous	-0.234	Destabilizing	0.961	D	0.486	neutral	None	None	None	None	N
S/T	0.0921	likely_benign	0.0904	benign	-0.27	Destabilizing	0.722	D	0.442	neutral	N	0.517576986	None	None	N
S/V	0.2081	likely_benign	0.2351	benign	-0.182	Destabilizing	0.923	D	0.506	neutral	None	None	None	None	N
S/W	0.3571	ambiguous	0.4093	ambiguous	-0.961	Destabilizing	0.996	D	0.658	neutral	None	None	None	None	N
S/Y	0.1903	likely_benign	0.2177	benign	-0.664	Destabilizing	0.983	D	0.574	neutral	D	0.596662405	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.