TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1154	3685;3686;3687	chr2:178781184;178781183;178781182	chr2:179645911;179645910;179645909
N2AB	1154	3685;3686;3687	chr2:178781184;178781183;178781182	chr2:179645911;179645910;179645909
N2A	1154	3685;3686;3687	chr2:178781184;178781183;178781182	chr2:179645911;179645910;179645909
N2B	1108	3547;3548;3549	chr2:178781184;178781183;178781182	chr2:179645911;179645910;179645909
Novex-1	1108	3547;3548;3549	chr2:178781184;178781183;178781182	chr2:179645911;179645910;179645909
Novex-2	1108	3547;3548;3549	chr2:178781184;178781183;178781182	chr2:179645911;179645910;179645909
Novex-3	1154	3685;3686;3687	chr2:178781184;178781183;178781182	chr2:179645911;179645910;179645909

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-4
• Domain position: 73
• Structural Position: 154
• Q(SASA): 0.0953
• 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
Y/H	None	None	1.0	D	0.801	0.858	0.714328772918	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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
Y/A	0.9995	likely_pathogenic	0.9996	pathogenic	-1.838	Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
Y/C	0.9958	likely_pathogenic	0.9967	pathogenic	-1.392	Destabilizing	1.0	D	0.881	deleterious	D	0.766369182	None	None	N
Y/D	0.9994	likely_pathogenic	0.9994	pathogenic	-2.537	Highly Destabilizing	1.0	D	0.897	deleterious	D	0.801159458	None	None	N
Y/E	0.9998	likely_pathogenic	0.9998	pathogenic	-2.287	Highly Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
Y/F	0.5625	ambiguous	0.5814	pathogenic	-0.596	Destabilizing	0.999	D	0.701	prob.neutral	D	0.639383628	None	None	N
Y/G	0.9981	likely_pathogenic	0.9983	pathogenic	-2.283	Highly Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
Y/H	0.9976	likely_pathogenic	0.9981	pathogenic	-1.999	Destabilizing	1.0	D	0.801	deleterious	D	0.801785381	None	None	N
Y/I	0.9912	likely_pathogenic	0.9904	pathogenic	-0.37	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
Y/K	0.9998	likely_pathogenic	0.9998	pathogenic	-1.517	Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
Y/L	0.9734	likely_pathogenic	0.9712	pathogenic	-0.37	Destabilizing	0.999	D	0.822	deleterious	None	None	None	None	N
Y/M	0.9953	likely_pathogenic	0.9955	pathogenic	-0.628	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
Y/N	0.9961	likely_pathogenic	0.9964	pathogenic	-2.399	Highly Destabilizing	1.0	D	0.894	deleterious	D	0.801159458	None	None	N
Y/P	0.9998	likely_pathogenic	0.9998	pathogenic	-0.874	Destabilizing	1.0	D	0.916	deleterious	None	None	None	None	N
Y/Q	0.9999	likely_pathogenic	0.9999	pathogenic	-1.904	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
Y/R	0.9994	likely_pathogenic	0.9994	pathogenic	-1.987	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
Y/S	0.9991	likely_pathogenic	0.9992	pathogenic	-2.681	Highly Destabilizing	1.0	D	0.897	deleterious	D	0.801159458	None	None	N
Y/T	0.9995	likely_pathogenic	0.9996	pathogenic	-2.279	Highly Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
Y/V	0.9873	likely_pathogenic	0.9861	pathogenic	-0.874	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
Y/W	0.9596	likely_pathogenic	0.9718	pathogenic	-0.027	Destabilizing	1.0	D	0.795	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.