TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18197	54814;54815;54816	chr2:178604098;178604097;178604096	chr2:179468825;179468824;179468823
N2AB	16556	49891;49892;49893	chr2:178604098;178604097;178604096	chr2:179468825;179468824;179468823
N2A	15629	47110;47111;47112	chr2:178604098;178604097;178604096	chr2:179468825;179468824;179468823
N2B	9132	27619;27620;27621	chr2:178604098;178604097;178604096	chr2:179468825;179468824;179468823
Novex-1	9257	27994;27995;27996	chr2:178604098;178604097;178604096	chr2:179468825;179468824;179468823
Novex-2	9324	28195;28196;28197	chr2:178604098;178604097;178604096	chr2:179468825;179468824;179468823
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-20
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.6349
• 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
P/A	rs1475050139	None	0.026	N	0.191	0.194	0.1749357433	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
P/A	rs1475050139	None	0.026	N	0.191	0.194	0.1749357433	gnomAD-4.0.0	6.58189E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.47167E-05	0	0
P/S	rs1475050139	None	0.811	N	0.442	0.281	0.235664433957	gnomAD-4.0.0	1.59361E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86331E-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
P/A	0.0921	likely_benign	0.078	benign	-0.342	Destabilizing	0.026	N	0.191	neutral	N	0.491508418	None	None	I
P/C	0.6935	likely_pathogenic	0.6134	pathogenic	-0.51	Destabilizing	0.997	D	0.575	neutral	None	None	None	None	I
P/D	0.5612	ambiguous	0.5177	ambiguous	-0.191	Destabilizing	0.988	D	0.457	neutral	None	None	None	None	I
P/E	0.36	ambiguous	0.3237	benign	-0.323	Destabilizing	0.919	D	0.461	neutral	None	None	None	None	I
P/F	0.6542	likely_pathogenic	0.5451	ambiguous	-0.734	Destabilizing	0.976	D	0.591	neutral	None	None	None	None	I
P/G	0.405	ambiguous	0.3319	benign	-0.443	Destabilizing	0.851	D	0.484	neutral	None	None	None	None	I
P/H	0.3238	likely_benign	0.2737	benign	-0.105	Destabilizing	0.999	D	0.558	neutral	None	None	None	None	I
P/I	0.3788	ambiguous	0.3151	benign	-0.237	Destabilizing	0.851	D	0.513	neutral	None	None	None	None	I
P/K	0.4337	ambiguous	0.3904	ambiguous	-0.203	Destabilizing	0.919	D	0.455	neutral	None	None	None	None	I
P/L	0.175	likely_benign	0.1323	benign	-0.237	Destabilizing	0.64	D	0.497	neutral	N	0.486553886	None	None	I
P/M	0.3365	likely_benign	0.2699	benign	-0.188	Destabilizing	0.307	N	0.333	neutral	None	None	None	None	I
P/N	0.3754	ambiguous	0.3299	benign	0.061	Stabilizing	0.988	D	0.573	neutral	None	None	None	None	I
P/Q	0.1997	likely_benign	0.1689	benign	-0.217	Destabilizing	0.984	D	0.512	neutral	N	0.470549545	None	None	I
P/R	0.3228	likely_benign	0.2873	benign	0.293	Stabilizing	0.984	D	0.561	neutral	N	0.516348148	None	None	I
P/S	0.1526	likely_benign	0.1247	benign	-0.283	Destabilizing	0.811	D	0.442	neutral	N	0.511710332	None	None	I
P/T	0.1166	likely_benign	0.0929	benign	-0.317	Destabilizing	0.896	D	0.481	neutral	N	0.482254217	None	None	I
P/V	0.2205	likely_benign	0.1872	benign	-0.238	Destabilizing	0.851	D	0.469	neutral	None	None	None	None	I
P/W	0.833	likely_pathogenic	0.7672	pathogenic	-0.803	Destabilizing	0.999	D	0.665	neutral	None	None	None	None	I
P/Y	0.6251	likely_pathogenic	0.5482	ambiguous	-0.473	Destabilizing	0.996	D	0.59	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.