TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8233	24922;24923;24924	chr2:178718409;178718408;178718407	chr2:179583136;179583135;179583134
N2AB	7916	23971;23972;23973	chr2:178718409;178718408;178718407	chr2:179583136;179583135;179583134
N2A	6989	21190;21191;21192	chr2:178718409;178718408;178718407	chr2:179583136;179583135;179583134
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-67
• Domain position: 63
• Structural Position: 144
• Q(SASA): 0.1267
• 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/N	None	None	0.051	N	0.247	0.289	0.242825505644	gnomAD-4.0.0	6.84224E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99489E-07	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	0.1147	likely_benign	0.1036	benign	-0.439	Destabilizing	0.007	N	0.189	neutral	None	None	None	None	N
S/C	0.1619	likely_benign	0.1566	benign	-1.002	Destabilizing	0.997	D	0.586	neutral	N	0.489826055	None	None	N
S/D	0.9196	likely_pathogenic	0.9237	pathogenic	-2.017	Highly Destabilizing	0.016	N	0.225	neutral	None	None	None	None	N
S/E	0.9651	likely_pathogenic	0.9637	pathogenic	-1.938	Destabilizing	0.525	D	0.485	neutral	None	None	None	None	N
S/F	0.9328	likely_pathogenic	0.9282	pathogenic	-0.854	Destabilizing	0.991	D	0.638	neutral	None	None	None	None	N
S/G	0.1558	likely_benign	0.1595	benign	-0.671	Destabilizing	0.454	N	0.459	neutral	N	0.507355437	None	None	N
S/H	0.9322	likely_pathogenic	0.9317	pathogenic	-1.19	Destabilizing	0.974	D	0.609	neutral	None	None	None	None	N
S/I	0.6322	likely_pathogenic	0.575	pathogenic	0.083	Stabilizing	0.934	D	0.644	neutral	N	0.483702585	None	None	N
S/K	0.9908	likely_pathogenic	0.9904	pathogenic	-0.491	Destabilizing	0.842	D	0.509	neutral	None	None	None	None	N
S/L	0.5042	ambiguous	0.4687	ambiguous	0.083	Stabilizing	0.842	D	0.557	neutral	None	None	None	None	N
S/M	0.6636	likely_pathogenic	0.6334	pathogenic	0.114	Stabilizing	0.998	D	0.601	neutral	None	None	None	None	N
S/N	0.4238	ambiguous	0.477	ambiguous	-1.081	Destabilizing	0.051	N	0.247	neutral	N	0.518876327	None	None	N
S/P	0.6869	likely_pathogenic	0.6386	pathogenic	-0.059	Destabilizing	0.974	D	0.631	neutral	None	None	None	None	N
S/Q	0.9613	likely_pathogenic	0.9579	pathogenic	-1.221	Destabilizing	0.974	D	0.607	neutral	None	None	None	None	N
S/R	0.9851	likely_pathogenic	0.9839	pathogenic	-0.456	Destabilizing	0.966	D	0.635	neutral	N	0.518876327	None	None	N
S/T	0.1472	likely_benign	0.1382	benign	-0.73	Destabilizing	0.051	N	0.222	neutral	N	0.497290745	None	None	N
S/V	0.5066	ambiguous	0.4303	ambiguous	-0.059	Destabilizing	0.728	D	0.562	neutral	None	None	None	None	N
S/W	0.9619	likely_pathogenic	0.9554	pathogenic	-1.077	Destabilizing	0.998	D	0.629	neutral	None	None	None	None	N
S/Y	0.8726	likely_pathogenic	0.8803	pathogenic	-0.595	Destabilizing	0.991	D	0.627	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.