TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28014	84265;84266;84267	chr2:178562092;178562091;178562090	chr2:179426819;179426818;179426817
N2AB	26373	79342;79343;79344	chr2:178562092;178562091;178562090	chr2:179426819;179426818;179426817
N2A	25446	76561;76562;76563	chr2:178562092;178562091;178562090	chr2:179426819;179426818;179426817
N2B	18949	57070;57071;57072	chr2:178562092;178562091;178562090	chr2:179426819;179426818;179426817
Novex-1	19074	57445;57446;57447	chr2:178562092;178562091;178562090	chr2:179426819;179426818;179426817
Novex-2	19141	57646;57647;57648	chr2:178562092;178562091;178562090	chr2:179426819;179426818;179426817
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-142
• Domain position: 52
• Structural Position: 130
• Q(SASA): 0.362
• 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/A	None	None	0.008	N	0.199	0.105	0.143124449307	gnomAD-4.0.0	1.59255E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43398E-05	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	0.1213	likely_benign	0.1246	benign	-0.423	Destabilizing	0.008	N	0.199	neutral	N	0.510105327	None	None	N
S/C	0.1452	likely_benign	0.1517	benign	-0.3	Destabilizing	0.989	D	0.47	neutral	None	None	None	None	N
S/D	0.3304	likely_benign	0.38	ambiguous	0.63	Stabilizing	0.775	D	0.347	neutral	None	None	None	None	N
S/E	0.5234	ambiguous	0.5645	pathogenic	0.546	Stabilizing	0.775	D	0.363	neutral	None	None	None	None	N
S/F	0.2669	likely_benign	0.2991	benign	-1.05	Destabilizing	0.961	D	0.563	neutral	None	None	None	None	N
S/G	0.0864	likely_benign	0.0928	benign	-0.524	Destabilizing	0.633	D	0.385	neutral	None	None	None	None	N
S/H	0.3802	ambiguous	0.4074	ambiguous	-0.987	Destabilizing	0.996	D	0.465	neutral	None	None	None	None	N
S/I	0.2903	likely_benign	0.3042	benign	-0.288	Destabilizing	0.858	D	0.549	neutral	None	None	None	None	N
S/K	0.6481	likely_pathogenic	0.6847	pathogenic	-0.237	Destabilizing	0.775	D	0.357	neutral	None	None	None	None	N
S/L	0.1206	likely_benign	0.1294	benign	-0.288	Destabilizing	0.565	D	0.453	neutral	N	0.485581106	None	None	N
S/M	0.2442	likely_benign	0.259	benign	-0.118	Destabilizing	0.989	D	0.46	neutral	None	None	None	None	N
S/N	0.1345	likely_benign	0.1406	benign	-0.035	Destabilizing	0.775	D	0.391	neutral	None	None	None	None	N
S/P	0.7006	likely_pathogenic	0.7173	pathogenic	-0.306	Destabilizing	0.949	D	0.423	neutral	N	0.50393885	None	None	N
S/Q	0.5167	ambiguous	0.5516	ambiguous	-0.223	Destabilizing	0.961	D	0.399	neutral	None	None	None	None	N
S/R	0.6014	likely_pathogenic	0.6581	pathogenic	-0.132	Destabilizing	0.923	D	0.428	neutral	None	None	None	None	N
S/T	0.072	likely_benign	0.0693	benign	-0.186	Destabilizing	0.003	N	0.171	neutral	N	0.432567263	None	None	N
S/V	0.2665	likely_benign	0.2765	benign	-0.306	Destabilizing	0.633	D	0.468	neutral	None	None	None	None	N
S/W	0.3965	ambiguous	0.4507	ambiguous	-1.046	Destabilizing	0.996	D	0.653	neutral	None	None	None	None	N
S/Y	0.2599	likely_benign	0.2866	benign	-0.752	Destabilizing	0.961	D	0.567	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.