TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3944	12055;12056;12057	chr2:178741403;178741402;178741401	chr2:179606130;179606129;179606128
N2AB	3627	11104;11105;11106	chr2:178741403;178741402;178741401	chr2:179606130;179606129;179606128
N2A	None	None	chr2:None	chr2:None
N2B	3581	10966;10967;10968	chr2:178741403;178741402;178741401	chr2:179606130;179606129;179606128
Novex-1	3706	11341;11342;11343	chr2:178741403;178741402;178741401	chr2:179606130;179606129;179606128
Novex-2	3773	11542;11543;11544	chr2:178741403;178741402;178741401	chr2:179606130;179606129;179606128
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Ig-28
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.1033
• 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
L/S	None	None	0.117	D	0.693	0.263	None	gnomAD-4.0.0	1.36835E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79886E-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
L/A	0.7631	likely_pathogenic	0.6824	pathogenic	-2.381	Highly Destabilizing	0.035	N	0.586	neutral	None	None	None	None	N
L/C	0.7427	likely_pathogenic	0.7136	pathogenic	-1.464	Destabilizing	0.935	D	0.666	neutral	None	None	None	None	N
L/D	0.9791	likely_pathogenic	0.9663	pathogenic	-2.578	Highly Destabilizing	0.555	D	0.747	deleterious	None	None	None	None	N
L/E	0.9079	likely_pathogenic	0.8594	pathogenic	-2.346	Highly Destabilizing	0.38	N	0.735	prob.delet.	None	None	None	None	N
L/F	0.1507	likely_benign	0.1636	benign	-1.342	Destabilizing	0.001	N	0.437	neutral	N	0.488034857	None	None	N
L/G	0.9058	likely_pathogenic	0.866	pathogenic	-2.925	Highly Destabilizing	0.38	N	0.733	prob.delet.	None	None	None	None	N
L/H	0.7755	likely_pathogenic	0.7267	pathogenic	-2.269	Highly Destabilizing	0.824	D	0.699	prob.neutral	None	None	None	None	N
L/I	0.1339	likely_benign	0.1281	benign	-0.807	Destabilizing	0.001	N	0.181	neutral	N	0.459292789	None	None	N
L/K	0.8569	likely_pathogenic	0.7946	pathogenic	-1.76	Destabilizing	0.38	N	0.707	prob.neutral	None	None	None	None	N
L/M	0.1641	likely_benign	0.1748	benign	-0.676	Destabilizing	0.555	D	0.631	neutral	None	None	None	None	N
L/N	0.9059	likely_pathogenic	0.8565	pathogenic	-2.078	Highly Destabilizing	0.555	D	0.74	deleterious	None	None	None	None	N
L/P	0.5933	likely_pathogenic	0.3967	ambiguous	-1.313	Destabilizing	0.001	N	0.615	neutral	None	None	None	None	N
L/Q	0.7213	likely_pathogenic	0.6358	pathogenic	-1.946	Destabilizing	0.555	D	0.678	prob.neutral	None	None	None	None	N
L/R	0.7739	likely_pathogenic	0.6942	pathogenic	-1.509	Destabilizing	0.555	D	0.713	prob.delet.	None	None	None	None	N
L/S	0.896	likely_pathogenic	0.8456	pathogenic	-2.773	Highly Destabilizing	0.117	N	0.693	prob.neutral	D	0.557151508	None	None	N
L/T	0.7926	likely_pathogenic	0.7058	pathogenic	-2.392	Highly Destabilizing	0.149	N	0.654	neutral	None	None	None	None	N
L/V	0.2094	likely_benign	0.1804	benign	-1.313	Destabilizing	None	N	0.215	neutral	D	0.54734741	None	None	N
L/W	0.4485	ambiguous	0.4683	ambiguous	-1.696	Destabilizing	0.824	D	0.673	neutral	None	None	None	None	N
L/Y	0.6602	likely_pathogenic	0.6657	pathogenic	-1.391	Destabilizing	0.235	N	0.731	prob.delet.	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.