TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29666	89221;89222;89223	chr2:178554115;178554114;178554113	chr2:179418842;179418841;179418840
N2AB	28025	84298;84299;84300	chr2:178554115;178554114;178554113	chr2:179418842;179418841;179418840
N2A	27098	81517;81518;81519	chr2:178554115;178554114;178554113	chr2:179418842;179418841;179418840
N2B	20601	62026;62027;62028	chr2:178554115;178554114;178554113	chr2:179418842;179418841;179418840
Novex-1	20726	62401;62402;62403	chr2:178554115;178554114;178554113	chr2:179418842;179418841;179418840
Novex-2	20793	62602;62603;62604	chr2:178554115;178554114;178554113	chr2:179418842;179418841;179418840
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-104
• Domain position: 34
• Structural Position: 36
• Q(SASA): 0.6587
• Predicted PPI site: I

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	None	N	0.097	0.102	0.110078149338	gnomAD-4.0.0	2.40065E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.62501E-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	0.0784	likely_benign	0.0802	benign	-0.629	Destabilizing	0.031	N	0.385	neutral	None	None	None	None	I
S/C	0.0859	likely_benign	0.0941	benign	-0.422	Destabilizing	0.828	D	0.393	neutral	N	0.473143211	None	None	I
S/D	0.2468	likely_benign	0.2739	benign	-0.035	Destabilizing	None	N	0.102	neutral	None	None	None	None	I
S/E	0.3632	ambiguous	0.377	ambiguous	-0.084	Destabilizing	0.016	N	0.372	neutral	None	None	None	None	I
S/F	0.1925	likely_benign	0.2082	benign	-0.993	Destabilizing	0.356	N	0.384	neutral	None	None	None	None	I
S/G	0.084	likely_benign	0.0964	benign	-0.817	Destabilizing	0.012	N	0.372	neutral	N	0.468775118	None	None	I
S/H	0.1955	likely_benign	0.2093	benign	-1.337	Destabilizing	0.214	N	0.403	neutral	None	None	None	None	I
S/I	0.1057	likely_benign	0.107	benign	-0.249	Destabilizing	0.295	N	0.4	neutral	N	0.458702566	None	None	I
S/K	0.3654	ambiguous	0.3747	ambiguous	-0.615	Destabilizing	0.001	N	0.115	neutral	None	None	None	None	I
S/L	0.0897	likely_benign	0.0842	benign	-0.249	Destabilizing	0.072	N	0.345	neutral	None	None	None	None	I
S/M	0.1546	likely_benign	0.1547	benign	0.091	Stabilizing	0.628	D	0.397	neutral	None	None	None	None	I
S/N	0.0807	likely_benign	0.0854	benign	-0.443	Destabilizing	None	N	0.097	neutral	N	0.46776116	None	None	I
S/P	0.4642	ambiguous	0.5326	ambiguous	-0.344	Destabilizing	0.136	N	0.423	neutral	None	None	None	None	I
S/Q	0.288	likely_benign	0.3036	benign	-0.685	Destabilizing	0.072	N	0.349	neutral	None	None	None	None	I
S/R	0.3201	likely_benign	0.3396	benign	-0.446	Destabilizing	None	N	0.213	neutral	N	0.503512136	None	None	I
S/T	0.061	likely_benign	0.0591	benign	-0.533	Destabilizing	0.012	N	0.305	neutral	N	0.38456738	None	None	I
S/V	0.1258	likely_benign	0.1263	benign	-0.344	Destabilizing	0.072	N	0.392	neutral	None	None	None	None	I
S/W	0.3374	likely_benign	0.3772	ambiguous	-0.937	Destabilizing	0.864	D	0.535	neutral	None	None	None	None	I
S/Y	0.1652	likely_benign	0.1792	benign	-0.682	Destabilizing	0.356	N	0.386	neutral	None	None	None	None	I

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.