TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5691	17296;17297;17298	chr2:178731804;178731803;178731802	chr2:179596531;179596530;179596529
N2AB	5374	16345;16346;16347	chr2:178731804;178731803;178731802	chr2:179596531;179596530;179596529
N2A	4447	13564;13565;13566	chr2:178731804;178731803;178731802	chr2:179596531;179596530;179596529
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-40
• Domain position: 55
• Structural Position: 135
• Q(SASA): 0.1694
• 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/P	None	None	0.896	N	0.653	0.374	0.797747263677	gnomAD-4.0.0	1.59122E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8583E-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	0.114	likely_benign	0.1321	benign	-1.686	Destabilizing	0.25	N	0.491	neutral	None	None	None	None	N
L/C	0.2997	likely_benign	0.3591	ambiguous	-0.919	Destabilizing	0.992	D	0.558	neutral	None	None	None	None	N
L/D	0.3474	ambiguous	0.4406	ambiguous	-1.274	Destabilizing	0.85	D	0.649	neutral	None	None	None	None	N
L/E	0.1578	likely_benign	0.1809	benign	-1.28	Destabilizing	0.447	N	0.609	neutral	None	None	None	None	N
L/F	0.0879	likely_benign	0.1086	benign	-1.211	Destabilizing	0.85	D	0.51	neutral	None	None	None	None	N
L/G	0.3018	likely_benign	0.3828	ambiguous	-2.005	Highly Destabilizing	0.617	D	0.61	neutral	None	None	None	None	N
L/H	0.0966	likely_benign	0.119	benign	-1.286	Destabilizing	0.977	D	0.633	neutral	None	None	None	None	N
L/I	0.0674	likely_benign	0.0727	benign	-0.884	Destabilizing	0.25	N	0.437	neutral	None	None	None	None	N
L/K	0.135	likely_benign	0.1464	benign	-1.215	Destabilizing	0.447	N	0.581	neutral	None	None	None	None	N
L/M	0.0802	likely_benign	0.0861	benign	-0.608	Destabilizing	0.036	N	0.253	neutral	N	0.496733385	None	None	N
L/N	0.1846	likely_benign	0.2227	benign	-0.975	Destabilizing	0.85	D	0.644	neutral	None	None	None	None	N
L/P	0.5861	likely_pathogenic	0.7962	pathogenic	-1.121	Destabilizing	0.896	D	0.653	neutral	N	0.49080749	None	None	N
L/Q	0.0754	likely_benign	0.0815	benign	-1.175	Destabilizing	0.036	N	0.437	neutral	N	0.45232646	None	None	N
L/R	0.0951	likely_benign	0.1043	benign	-0.593	Destabilizing	0.681	D	0.625	neutral	N	0.457558921	None	None	N
L/S	0.1149	likely_benign	0.1436	benign	-1.545	Destabilizing	0.059	N	0.451	neutral	None	None	None	None	N
L/T	0.0955	likely_benign	0.1058	benign	-1.443	Destabilizing	0.021	N	0.367	neutral	None	None	None	None	N
L/V	0.065	likely_benign	0.0693	benign	-1.121	Destabilizing	0.016	N	0.175	neutral	N	0.428161521	None	None	N
L/W	0.1601	likely_benign	0.2118	benign	-1.301	Destabilizing	0.992	D	0.635	neutral	None	None	None	None	N
L/Y	0.1906	likely_benign	0.2388	benign	-1.093	Destabilizing	0.92	D	0.58	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.