TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30877	92854;92855;92856	chr2:178548997;178548996;178548995	chr2:179413724;179413723;179413722
N2AB	29236	87931;87932;87933	chr2:178548997;178548996;178548995	chr2:179413724;179413723;179413722
N2A	28309	85150;85151;85152	chr2:178548997;178548996;178548995	chr2:179413724;179413723;179413722
N2B	21812	65659;65660;65661	chr2:178548997;178548996;178548995	chr2:179413724;179413723;179413722
Novex-1	21937	66034;66035;66036	chr2:178548997;178548996;178548995	chr2:179413724;179413723;179413722
Novex-2	22004	66235;66236;66237	chr2:178548997;178548996;178548995	chr2:179413724;179413723;179413722
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-113
• Domain position: 57
• Structural Position: 83
• Q(SASA): 0.6854
• 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
V/M	None	None	0.81	N	0.508	0.163	0.254244900254	gnomAD-4.0.0	3.18218E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85786E-06	1.43279E-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
V/A	0.1566	likely_benign	0.1537	benign	-0.645	Destabilizing	0.334	N	0.436	neutral	N	0.419738746	None	None	I
V/C	0.5782	likely_pathogenic	0.5984	pathogenic	-0.59	Destabilizing	0.992	D	0.459	neutral	None	None	None	None	I
V/D	0.3503	ambiguous	0.3142	benign	-0.34	Destabilizing	0.972	D	0.499	neutral	None	None	None	None	I
V/E	0.2702	likely_benign	0.257	benign	-0.429	Destabilizing	0.896	D	0.49	neutral	N	0.385412742	None	None	I
V/F	0.1361	likely_benign	0.1398	benign	-0.725	Destabilizing	0.739	D	0.445	neutral	None	None	None	None	I
V/G	0.1552	likely_benign	0.1487	benign	-0.813	Destabilizing	0.896	D	0.474	neutral	N	0.4324974	None	None	I
V/H	0.4296	ambiguous	0.4336	ambiguous	-0.269	Destabilizing	0.992	D	0.505	neutral	None	None	None	None	I
V/I	0.0645	likely_benign	0.0648	benign	-0.339	Destabilizing	0.002	N	0.114	neutral	None	None	None	None	I
V/K	0.2606	likely_benign	0.2589	benign	-0.527	Destabilizing	0.92	D	0.487	neutral	None	None	None	None	I
V/L	0.1162	likely_benign	0.1194	benign	-0.339	Destabilizing	0.002	N	0.104	neutral	N	0.440788809	None	None	I
V/M	0.0995	likely_benign	0.1118	benign	-0.395	Destabilizing	0.81	D	0.508	neutral	N	0.458529208	None	None	I
V/N	0.2141	likely_benign	0.204	benign	-0.27	Destabilizing	0.972	D	0.495	neutral	None	None	None	None	I
V/P	0.2445	likely_benign	0.2261	benign	-0.406	Destabilizing	0.972	D	0.491	neutral	None	None	None	None	I
V/Q	0.2315	likely_benign	0.2347	benign	-0.492	Destabilizing	0.972	D	0.486	neutral	None	None	None	None	I
V/R	0.2233	likely_benign	0.2241	benign	0.013	Stabilizing	0.92	D	0.495	neutral	None	None	None	None	I
V/S	0.1662	likely_benign	0.1623	benign	-0.665	Destabilizing	0.92	D	0.449	neutral	None	None	None	None	I
V/T	0.1534	likely_benign	0.1592	benign	-0.65	Destabilizing	0.617	D	0.425	neutral	None	None	None	None	I
V/W	0.6443	likely_pathogenic	0.6791	pathogenic	-0.81	Destabilizing	0.992	D	0.595	neutral	None	None	None	None	I
V/Y	0.4145	ambiguous	0.437	ambiguous	-0.521	Destabilizing	0.92	D	0.469	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.