TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3823	11692;11693;11694	chr2:178741766;178741765;178741764	chr2:179606493;179606492;179606491
N2AB	3506	10741;10742;10743	chr2:178741766;178741765;178741764	chr2:179606493;179606492;179606491
N2A	None	None	chr2:None	chr2:None
N2B	3460	10603;10604;10605	chr2:178741766;178741765;178741764	chr2:179606493;179606492;179606491
Novex-1	3585	10978;10979;10980	chr2:178741766;178741765;178741764	chr2:179606493;179606492;179606491
Novex-2	3652	11179;11180;11181	chr2:178741766;178741765;178741764	chr2:179606493;179606492;179606491
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-27
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.5473
• 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
I/F	rs1233837931	-0.561	0.175	D	0.241	0.233	None	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
I/F	rs1233837931	-0.561	0.175	D	0.241	0.233	None	gnomAD-4.0.0	1.59176E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85879E-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
I/A	0.3093	likely_benign	0.2258	benign	-0.848	Destabilizing	0.025	N	0.146	neutral	None	None	None	None	I
I/C	0.5515	ambiguous	0.5414	ambiguous	-0.831	Destabilizing	0.667	D	0.279	neutral	None	None	None	None	I
I/D	0.6202	likely_pathogenic	0.4906	ambiguous	-0.216	Destabilizing	0.124	N	0.299	neutral	None	None	None	None	I
I/E	0.415	ambiguous	0.2928	benign	-0.256	Destabilizing	0.002	N	0.181	neutral	None	None	None	None	I
I/F	0.1554	likely_benign	0.1262	benign	-0.546	Destabilizing	0.175	N	0.241	neutral	D	0.525418572	None	None	I
I/G	0.5657	likely_pathogenic	0.4342	ambiguous	-1.07	Destabilizing	0.22	N	0.299	neutral	None	None	None	None	I
I/H	0.3765	ambiguous	0.2798	benign	-0.112	Destabilizing	0.859	D	0.266	neutral	None	None	None	None	I
I/K	0.2228	likely_benign	0.1467	benign	-0.568	Destabilizing	0.124	N	0.298	neutral	None	None	None	None	I
I/L	0.0973	likely_benign	0.079	benign	-0.358	Destabilizing	None	N	0.053	neutral	N	0.446427474	None	None	I
I/M	0.1	likely_benign	0.0894	benign	-0.513	Destabilizing	0.427	N	0.268	neutral	N	0.449096056	None	None	I
I/N	0.2264	likely_benign	0.162	benign	-0.524	Destabilizing	0.175	N	0.382	neutral	D	0.525611982	None	None	I
I/P	0.6974	likely_pathogenic	0.6483	pathogenic	-0.489	Destabilizing	0.364	N	0.36	neutral	None	None	None	None	I
I/Q	0.2781	likely_benign	0.1936	benign	-0.678	Destabilizing	0.22	N	0.371	neutral	None	None	None	None	I
I/R	0.1485	likely_benign	0.1011	benign	0.007	Stabilizing	0.22	N	0.361	neutral	None	None	None	None	I
I/S	0.2316	likely_benign	0.1729	benign	-1.052	Destabilizing	0.042	N	0.237	neutral	N	0.453916465	None	None	I
I/T	0.1524	likely_benign	0.1074	benign	-0.976	Destabilizing	None	N	0.095	neutral	N	0.433536328	None	None	I
I/V	0.0816	likely_benign	0.0744	benign	-0.489	Destabilizing	None	N	0.074	neutral	N	0.438340762	None	None	I
I/W	0.6379	likely_pathogenic	0.5773	pathogenic	-0.568	Destabilizing	0.958	D	0.259	neutral	None	None	None	None	I
I/Y	0.404	ambiguous	0.359	ambiguous	-0.344	Destabilizing	0.667	D	0.377	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.