TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13958	42097;42098;42099	chr2:178635452;178635451;178635450	chr2:179500179;179500178;179500177
N2AB	12317	37174;37175;37176	chr2:178635452;178635451;178635450	chr2:179500179;179500178;179500177
N2A	11390	34393;34394;34395	chr2:178635452;178635451;178635450	chr2:179500179;179500178;179500177
N2B	4893	14902;14903;14904	chr2:178635452;178635451;178635450	chr2:179500179;179500178;179500177
Novex-1	5018	15277;15278;15279	chr2:178635452;178635451;178635450	chr2:179500179;179500178;179500177
Novex-2	5085	15478;15479;15480	chr2:178635452;178635451;178635450	chr2:179500179;179500178;179500177
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-89
• Domain position: 83
• Structural Position: 178
• Q(SASA): 0.1974
• 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/V	None	None	0.997	D	0.549	0.451	0.690638299042	gnomAD-4.0.0	6.87166E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.01837E-07	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	0.9756	likely_pathogenic	0.9769	pathogenic	-2.545	Highly Destabilizing	0.998	D	0.753	deleterious	None	None	None	None	N
L/C	0.9528	likely_pathogenic	0.9545	pathogenic	-1.692	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
L/D	0.9996	likely_pathogenic	0.9996	pathogenic	-3.14	Highly Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
L/E	0.9979	likely_pathogenic	0.9979	pathogenic	-2.875	Highly Destabilizing	0.999	D	0.86	deleterious	None	None	None	None	N
L/F	0.8854	likely_pathogenic	0.8697	pathogenic	-1.521	Destabilizing	0.999	D	0.752	deleterious	None	None	None	None	N
L/G	0.9939	likely_pathogenic	0.9949	pathogenic	-3.119	Highly Destabilizing	0.999	D	0.869	deleterious	None	None	None	None	N
L/H	0.9968	likely_pathogenic	0.997	pathogenic	-2.749	Highly Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
L/I	0.4137	ambiguous	0.3431	ambiguous	-0.856	Destabilizing	0.998	D	0.563	neutral	None	None	None	None	N
L/K	0.9968	likely_pathogenic	0.9966	pathogenic	-1.9	Destabilizing	0.999	D	0.905	deleterious	None	None	None	None	N
L/M	0.5423	ambiguous	0.4897	ambiguous	-0.805	Destabilizing	0.999	D	0.763	deleterious	D	0.650239484	None	None	N
L/N	0.9974	likely_pathogenic	0.9974	pathogenic	-2.38	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
L/P	0.9985	likely_pathogenic	0.9985	pathogenic	-1.404	Destabilizing	1.0	D	0.865	deleterious	D	0.666943143	None	None	N
L/Q	0.9952	likely_pathogenic	0.9947	pathogenic	-2.163	Highly Destabilizing	1.0	D	0.887	deleterious	D	0.666863146	None	None	N
L/R	0.994	likely_pathogenic	0.994	pathogenic	-1.75	Destabilizing	0.999	D	0.893	deleterious	D	0.666863146	None	None	N
L/S	0.998	likely_pathogenic	0.9981	pathogenic	-3.013	Highly Destabilizing	0.999	D	0.899	deleterious	None	None	None	None	N
L/T	0.9873	likely_pathogenic	0.9879	pathogenic	-2.599	Highly Destabilizing	0.999	D	0.847	deleterious	None	None	None	None	N
L/V	0.5222	ambiguous	0.4647	ambiguous	-1.404	Destabilizing	0.997	D	0.549	neutral	D	0.647243714	None	None	N
L/W	0.9922	likely_pathogenic	0.9928	pathogenic	-2.029	Highly Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
L/Y	0.988	likely_pathogenic	0.9881	pathogenic	-1.711	Destabilizing	0.999	D	0.861	deleterious	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.