TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13762	41509;41510;41511	chr2:178636443;178636442;178636441	chr2:179501170;179501169;179501168
N2AB	12121	36586;36587;36588	chr2:178636443;178636442;178636441	chr2:179501170;179501169;179501168
N2A	11194	33805;33806;33807	chr2:178636443;178636442;178636441	chr2:179501170;179501169;179501168
N2B	4697	14314;14315;14316	chr2:178636443;178636442;178636441	chr2:179501170;179501169;179501168
Novex-1	4822	14689;14690;14691	chr2:178636443;178636442;178636441	chr2:179501170;179501169;179501168
Novex-2	4889	14890;14891;14892	chr2:178636443;178636442;178636441	chr2:179501170;179501169;179501168
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-87
• Domain position: 79
• Structural Position: 161
• Q(SASA): 0.6797
• 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/V	None	None	0.998	N	0.468	0.188	0.158396225186	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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	0.7673	likely_pathogenic	0.792	pathogenic	-0.756	Destabilizing	0.996	D	0.474	neutral	None	None	None	None	I
L/C	0.9637	likely_pathogenic	0.9619	pathogenic	-0.627	Destabilizing	1.0	D	0.479	neutral	None	None	None	None	I
L/D	0.9764	likely_pathogenic	0.9834	pathogenic	-0.022	Destabilizing	0.995	D	0.546	neutral	None	None	None	None	I
L/E	0.9355	likely_pathogenic	0.9502	pathogenic	-0.085	Destabilizing	0.998	D	0.547	neutral	None	None	None	None	I
L/F	0.7198	likely_pathogenic	0.7609	pathogenic	-0.589	Destabilizing	0.999	D	0.475	neutral	N	0.447823222	None	None	I
L/G	0.9375	likely_pathogenic	0.9478	pathogenic	-0.969	Destabilizing	0.998	D	0.526	neutral	None	None	None	None	I
L/H	0.8543	likely_pathogenic	0.8783	pathogenic	-0.281	Destabilizing	1.0	D	0.575	neutral	None	None	None	None	I
L/I	0.3831	ambiguous	0.3942	ambiguous	-0.303	Destabilizing	0.999	D	0.502	neutral	None	None	None	None	I
L/K	0.8944	likely_pathogenic	0.8987	pathogenic	-0.433	Destabilizing	0.998	D	0.502	neutral	None	None	None	None	I
L/M	0.4112	ambiguous	0.4211	ambiguous	-0.369	Destabilizing	0.999	D	0.511	neutral	N	0.428996272	None	None	I
L/N	0.7239	likely_pathogenic	0.7675	pathogenic	-0.213	Destabilizing	0.611	D	0.367	neutral	None	None	None	None	I
L/P	0.9856	likely_pathogenic	0.9875	pathogenic	-0.42	Destabilizing	1.0	D	0.563	neutral	None	None	None	None	I
L/Q	0.7379	likely_pathogenic	0.7736	pathogenic	-0.39	Destabilizing	0.999	D	0.533	neutral	None	None	None	None	I
L/R	0.8487	likely_pathogenic	0.8536	pathogenic	0.058	Stabilizing	0.999	D	0.529	neutral	None	None	None	None	I
L/S	0.8566	likely_pathogenic	0.884	pathogenic	-0.737	Destabilizing	0.989	D	0.5	neutral	N	0.393752438	None	None	I
L/T	0.8088	likely_pathogenic	0.8296	pathogenic	-0.686	Destabilizing	0.992	D	0.441	neutral	None	None	None	None	I
L/V	0.4516	ambiguous	0.4561	ambiguous	-0.42	Destabilizing	0.998	D	0.468	neutral	N	0.445527932	None	None	I
L/W	0.8681	likely_pathogenic	0.8712	pathogenic	-0.627	Destabilizing	1.0	D	0.569	neutral	N	0.428996272	None	None	I
L/Y	0.8778	likely_pathogenic	0.8984	pathogenic	-0.379	Destabilizing	1.0	D	0.451	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.