TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7192	21799;21800;21801	chr2:178723526;178723525;178723524	chr2:179588253;179588252;179588251
N2AB	6875	20848;20849;20850	chr2:178723526;178723525;178723524	chr2:179588253;179588252;179588251
N2A	5948	18067;18068;18069	chr2:178723526;178723525;178723524	chr2:179588253;179588252;179588251
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-56
• Domain position: 56
• Structural Position: 136
• Q(SASA): 0.1239
• 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
A/T	rs1212601280	None	0.022	N	0.473	0.16	0.0884992946249	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
A/T	rs1212601280	None	0.022	N	0.473	0.16	0.0884992946249	gnomAD-4.0.0	7.43847E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.01729E-05	0	0
A/V	rs1560705548	None	0.012	N	0.491	0.179	0.177238962908	gnomAD-4.0.0	1.59242E-06	None	None	None	None	N	None	0	0	None	0	2.77716E-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
A/C	0.6727	likely_pathogenic	0.6458	pathogenic	-0.617	Destabilizing	0.998	D	0.781	deleterious	None	None	None	None	N
A/D	0.9377	likely_pathogenic	0.9145	pathogenic	-1.543	Destabilizing	0.949	D	0.795	deleterious	None	None	None	None	N
A/E	0.8601	likely_pathogenic	0.8227	pathogenic	-1.346	Destabilizing	0.801	D	0.797	deleterious	N	0.508061446	None	None	N
A/F	0.711	likely_pathogenic	0.6842	pathogenic	-0.415	Destabilizing	0.974	D	0.811	deleterious	None	None	None	None	N
A/G	0.3087	likely_benign	0.2689	benign	-1.169	Destabilizing	0.801	D	0.748	deleterious	N	0.459595496	None	None	N
A/H	0.9266	likely_pathogenic	0.9104	pathogenic	-1.698	Destabilizing	0.998	D	0.783	deleterious	None	None	None	None	N
A/I	0.4877	ambiguous	0.4544	ambiguous	0.615	Stabilizing	0.067	N	0.633	neutral	None	None	None	None	N
A/K	0.9443	likely_pathogenic	0.9273	pathogenic	-0.647	Destabilizing	0.842	D	0.801	deleterious	None	None	None	None	N
A/L	0.3724	ambiguous	0.3502	ambiguous	0.615	Stabilizing	0.525	D	0.747	deleterious	None	None	None	None	N
A/M	0.4192	ambiguous	0.3931	ambiguous	0.354	Stabilizing	0.974	D	0.795	deleterious	None	None	None	None	N
A/N	0.873	likely_pathogenic	0.8351	pathogenic	-0.888	Destabilizing	0.949	D	0.801	deleterious	None	None	None	None	N
A/P	0.9483	likely_pathogenic	0.9348	pathogenic	0.229	Stabilizing	0.966	D	0.815	deleterious	N	0.506175934	None	None	N
A/Q	0.8595	likely_pathogenic	0.8365	pathogenic	-0.667	Destabilizing	0.974	D	0.817	deleterious	None	None	None	None	N
A/R	0.8923	likely_pathogenic	0.8701	pathogenic	-0.9	Destabilizing	0.949	D	0.815	deleterious	None	None	None	None	N
A/S	0.2012	likely_benign	0.1865	benign	-1.349	Destabilizing	0.136	N	0.533	neutral	N	0.432368822	None	None	N
A/T	0.1456	likely_benign	0.133	benign	-1.014	Destabilizing	0.022	N	0.473	neutral	N	0.456400475	None	None	N
A/V	0.2009	likely_benign	0.1894	benign	0.229	Stabilizing	0.012	N	0.491	neutral	N	0.472023288	None	None	N
A/W	0.9452	likely_pathogenic	0.9374	pathogenic	-1.199	Destabilizing	0.998	D	0.812	deleterious	None	None	None	None	N
A/Y	0.8612	likely_pathogenic	0.8374	pathogenic	-0.56	Destabilizing	0.991	D	0.814	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.