TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33304	100135;100136;100137	chr2:178537199;178537198;178537197	chr2:179401926;179401925;179401924
N2AB	31663	95212;95213;95214	chr2:178537199;178537198;178537197	chr2:179401926;179401925;179401924
N2A	30736	92431;92432;92433	chr2:178537199;178537198;178537197	chr2:179401926;179401925;179401924
N2B	24239	72940;72941;72942	chr2:178537199;178537198;178537197	chr2:179401926;179401925;179401924
Novex-1	24364	73315;73316;73317	chr2:178537199;178537198;178537197	chr2:179401926;179401925;179401924
Novex-2	24431	73516;73517;73518	chr2:178537199;178537198;178537197	chr2:179401926;179401925;179401924
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: Fn3-130
• Domain position: 15
• Structural Position: 16
• Q(SASA): 0.32
• 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/S	rs1691995704	None	1.0	N	0.775	0.511	0.645115249394	gnomAD-4.0.0	1.59635E-06	None	None	None	None	I	None	0	0	None	0	2.7767E-05	None	0	0	0	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	0.701	likely_pathogenic	0.6807	pathogenic	-1.204	Destabilizing	0.999	D	0.67	neutral	None	None	None	None	I
L/C	0.8754	likely_pathogenic	0.8603	pathogenic	-0.761	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
L/D	0.9524	likely_pathogenic	0.9367	pathogenic	-0.417	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	I
L/E	0.8155	likely_pathogenic	0.7948	pathogenic	-0.463	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	I
L/F	0.4092	ambiguous	0.3523	ambiguous	-0.941	Destabilizing	1.0	D	0.718	prob.delet.	N	0.476498893	None	None	I
L/G	0.8187	likely_pathogenic	0.8014	pathogenic	-1.465	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
L/H	0.7081	likely_pathogenic	0.6739	pathogenic	-0.682	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	I
L/I	0.3418	ambiguous	0.3143	benign	-0.597	Destabilizing	0.999	D	0.464	neutral	None	None	None	None	I
L/K	0.7404	likely_pathogenic	0.7336	pathogenic	-0.626	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
L/M	0.2745	likely_benign	0.253	benign	-0.442	Destabilizing	1.0	D	0.707	prob.neutral	N	0.495007296	None	None	I
L/N	0.764	likely_pathogenic	0.7241	pathogenic	-0.372	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
L/P	0.9517	likely_pathogenic	0.9375	pathogenic	-0.766	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
L/Q	0.5027	ambiguous	0.492	ambiguous	-0.602	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
L/R	0.6695	likely_pathogenic	0.6584	pathogenic	-0.058	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	I
L/S	0.7222	likely_pathogenic	0.6761	pathogenic	-0.987	Destabilizing	1.0	D	0.775	deleterious	N	0.399688761	None	None	I
L/T	0.5273	ambiguous	0.4967	ambiguous	-0.918	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
L/V	0.3648	ambiguous	0.3267	benign	-0.766	Destabilizing	0.999	D	0.462	neutral	N	0.476152177	None	None	I
L/W	0.7484	likely_pathogenic	0.7021	pathogenic	-0.939	Destabilizing	1.0	D	0.716	prob.delet.	N	0.467167334	None	None	I
L/Y	0.7897	likely_pathogenic	0.7353	pathogenic	-0.701	Destabilizing	1.0	D	0.763	deleterious	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.