TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14906	44941;44942;44943	chr2:178624564;178624563;178624562	chr2:179489291;179489290;179489289
N2AB	13265	40018;40019;40020	chr2:178624564;178624563;178624562	chr2:179489291;179489290;179489289
N2A	12338	37237;37238;37239	chr2:178624564;178624563;178624562	chr2:179489291;179489290;179489289
N2B	5841	17746;17747;17748	chr2:178624564;178624563;178624562	chr2:179489291;179489290;179489289
Novex-1	5966	18121;18122;18123	chr2:178624564;178624563;178624562	chr2:179489291;179489290;179489289
Novex-2	6033	18322;18323;18324	chr2:178624564;178624563;178624562	chr2:179489291;179489290;179489289
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-100
• Domain position: 54
• Structural Position: 135
• Q(SASA): 0.226
• 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/L	None	None	0.906	N	0.477	0.218	0.410734915765	gnomAD-4.0.0	1.59336E-06	None	None	None	None	N	None	0	0	None	0	2.78164E-05	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	0.3509	ambiguous	0.3136	benign	-1.735	Destabilizing	0.826	D	0.421	neutral	N	0.504486228	None	None	N
V/C	0.8064	likely_pathogenic	0.8205	pathogenic	-1.198	Destabilizing	0.999	D	0.497	neutral	None	None	None	None	N
V/D	0.528	ambiguous	0.5131	ambiguous	-2.314	Highly Destabilizing	0.988	D	0.616	neutral	N	0.504080339	None	None	N
V/E	0.3713	ambiguous	0.3469	ambiguous	-2.32	Highly Destabilizing	0.939	D	0.567	neutral	None	None	None	None	N
V/F	0.2065	likely_benign	0.1924	benign	-1.413	Destabilizing	0.996	D	0.543	neutral	N	0.502374388	None	None	N
V/G	0.3073	likely_benign	0.2928	benign	-2.044	Highly Destabilizing	0.959	D	0.594	neutral	N	0.506924587	None	None	N
V/H	0.5801	likely_pathogenic	0.5616	ambiguous	-1.602	Destabilizing	0.999	D	0.607	neutral	None	None	None	None	N
V/I	0.0841	likely_benign	0.0829	benign	-0.969	Destabilizing	0.986	D	0.474	neutral	N	0.459485943	None	None	N
V/K	0.2347	likely_benign	0.2299	benign	-1.503	Destabilizing	0.079	N	0.294	neutral	None	None	None	None	N
V/L	0.2321	likely_benign	0.2221	benign	-0.969	Destabilizing	0.906	D	0.477	neutral	N	0.484499307	None	None	N
V/M	0.2047	likely_benign	0.1951	benign	-0.692	Destabilizing	0.997	D	0.473	neutral	None	None	None	None	N
V/N	0.3588	ambiguous	0.3409	ambiguous	-1.349	Destabilizing	0.991	D	0.616	neutral	None	None	None	None	N
V/P	0.9173	likely_pathogenic	0.9139	pathogenic	-1.194	Destabilizing	0.997	D	0.592	neutral	None	None	None	None	N
V/Q	0.3105	likely_benign	0.2915	benign	-1.58	Destabilizing	0.982	D	0.585	neutral	None	None	None	None	N
V/R	0.2559	likely_benign	0.249	benign	-0.901	Destabilizing	0.046	N	0.449	neutral	None	None	None	None	N
V/S	0.3451	ambiguous	0.3157	benign	-1.756	Destabilizing	0.939	D	0.567	neutral	None	None	None	None	N
V/T	0.2802	likely_benign	0.2681	benign	-1.671	Destabilizing	0.969	D	0.445	neutral	None	None	None	None	N
V/W	0.8167	likely_pathogenic	0.8308	pathogenic	-1.642	Destabilizing	0.999	D	0.652	neutral	None	None	None	None	N
V/Y	0.5639	ambiguous	0.5606	ambiguous	-1.383	Destabilizing	0.997	D	0.541	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.