TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19192	57799;57800;57801	chr2:178595780;178595779;178595778	chr2:179460507;179460506;179460505
N2AB	17551	52876;52877;52878	chr2:178595780;178595779;178595778	chr2:179460507;179460506;179460505
N2A	16624	50095;50096;50097	chr2:178595780;178595779;178595778	chr2:179460507;179460506;179460505
N2B	10127	30604;30605;30606	chr2:178595780;178595779;178595778	chr2:179460507;179460506;179460505
Novex-1	10252	30979;30980;30981	chr2:178595780;178595779;178595778	chr2:179460507;179460506;179460505
Novex-2	10319	31180;31181;31182	chr2:178595780;178595779;178595778	chr2:179460507;179460506;179460505
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Fn3-27
• Domain position: 10
• Structural Position: 11
• Q(SASA): 0.435
• 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
L/P	rs1338687639	None	0.295	N	0.599	0.213	0.576807342058	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/P	rs1338687639	None	0.295	N	0.599	0.213	0.576807342058	gnomAD-4.0.0	1.86659E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.54908E-06	0	0
L/V	None	None	0.001	N	0.218	0.064	0.342400092842	gnomAD-4.0.0	4.82498E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.64788E-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	0.105	likely_benign	0.1023	benign	-1.252	Destabilizing	None	N	0.281	neutral	None	None	None	None	I
L/C	0.28	likely_benign	0.2981	benign	-0.505	Destabilizing	0.864	D	0.534	neutral	None	None	None	None	I
L/D	0.3544	ambiguous	0.3661	ambiguous	-0.742	Destabilizing	0.072	N	0.564	neutral	None	None	None	None	I
L/E	0.1367	likely_benign	0.1418	benign	-0.754	Destabilizing	0.038	N	0.485	neutral	None	None	None	None	I
L/F	0.0902	likely_benign	0.0916	benign	-0.891	Destabilizing	0.356	N	0.501	neutral	None	None	None	None	I
L/G	0.3105	likely_benign	0.3316	benign	-1.536	Destabilizing	0.031	N	0.463	neutral	None	None	None	None	I
L/H	0.0879	likely_benign	0.0975	benign	-0.752	Destabilizing	0.001	N	0.411	neutral	None	None	None	None	I
L/I	0.0679	likely_benign	0.0659	benign	-0.559	Destabilizing	0.029	N	0.37	neutral	N	0.427491438	None	None	I
L/K	0.1203	likely_benign	0.1244	benign	-0.717	Destabilizing	0.016	N	0.473	neutral	None	None	None	None	I
L/M	0.0884	likely_benign	0.0816	benign	-0.431	Destabilizing	0.356	N	0.484	neutral	None	None	None	None	I
L/N	0.1896	likely_benign	0.1867	benign	-0.465	Destabilizing	0.072	N	0.553	neutral	None	None	None	None	I
L/P	0.6472	likely_pathogenic	0.7562	pathogenic	-0.758	Destabilizing	0.295	N	0.599	neutral	N	0.455968905	None	None	I
L/Q	0.0702	likely_benign	0.0704	benign	-0.637	Destabilizing	None	N	0.413	neutral	N	0.397787394	None	None	I
L/R	0.0976	likely_benign	0.1076	benign	-0.168	Destabilizing	None	N	0.419	neutral	N	0.399942264	None	None	I
L/S	0.1052	likely_benign	0.1045	benign	-0.985	Destabilizing	0.001	N	0.353	neutral	None	None	None	None	I
L/T	0.084	likely_benign	0.0801	benign	-0.883	Destabilizing	0.016	N	0.435	neutral	None	None	None	None	I
L/V	0.0653	likely_benign	0.0632	benign	-0.758	Destabilizing	0.001	N	0.218	neutral	N	0.394357512	None	None	I
L/W	0.1876	likely_benign	0.2121	benign	-0.969	Destabilizing	0.864	D	0.551	neutral	None	None	None	None	I
L/Y	0.2057	likely_benign	0.2085	benign	-0.732	Destabilizing	0.214	N	0.613	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.