TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8711	26356;26357;26358	chr2:178715055;178715054;178715053	chr2:179579782;179579781;179579780
N2AB	8394	25405;25406;25407	chr2:178715055;178715054;178715053	chr2:179579782;179579781;179579780
N2A	7467	22624;22625;22626	chr2:178715055;178715054;178715053	chr2:179579782;179579781;179579780
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: G
• RefSeq wild type transcript codon: GGG
• RefSeq wild type template codon: CCC
• Domain: Ig-72
• Domain position: 69
• Structural Position: 152
• Q(SASA): 0.2464
• 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
G/R	rs1220276093	-0.193	1.0	D	0.833	0.72	0.874928965229	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
G/R	rs1220276093	-0.193	1.0	D	0.833	0.72	0.874928965229	gnomAD-4.0.0	1.59173E-06	None	None	None	None	N	None	5.66251E-05	0	None	0	0	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
G/A	0.3954	ambiguous	0.5384	ambiguous	-0.491	Destabilizing	1.0	D	0.78	deleterious	D	0.587470787	None	None	N
G/C	0.7603	likely_pathogenic	0.863	pathogenic	-0.786	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
G/D	0.827	likely_pathogenic	0.8918	pathogenic	-0.504	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
G/E	0.8888	likely_pathogenic	0.9344	pathogenic	-0.562	Destabilizing	1.0	D	0.839	deleterious	D	0.656230808	None	None	N
G/F	0.9722	likely_pathogenic	0.9819	pathogenic	-0.821	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
G/H	0.9492	likely_pathogenic	0.9698	pathogenic	-0.999	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
G/I	0.9642	likely_pathogenic	0.9819	pathogenic	-0.147	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
G/K	0.9488	likely_pathogenic	0.9693	pathogenic	-0.962	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
G/L	0.9347	likely_pathogenic	0.9583	pathogenic	-0.147	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
G/M	0.9554	likely_pathogenic	0.9752	pathogenic	-0.238	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
G/N	0.8865	likely_pathogenic	0.9255	pathogenic	-0.668	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
G/P	0.9942	likely_pathogenic	0.9967	pathogenic	-0.22	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
G/Q	0.8919	likely_pathogenic	0.9325	pathogenic	-0.799	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
G/R	0.861	likely_pathogenic	0.9144	pathogenic	-0.704	Destabilizing	1.0	D	0.833	deleterious	D	0.656029004	None	None	N
G/S	0.3226	likely_benign	0.451	ambiguous	-0.978	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
G/T	0.7888	likely_pathogenic	0.8668	pathogenic	-0.937	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
G/V	0.9102	likely_pathogenic	0.9508	pathogenic	-0.22	Destabilizing	1.0	D	0.783	deleterious	D	0.656230808	None	None	N
G/W	0.9358	likely_pathogenic	0.9576	pathogenic	-1.167	Destabilizing	1.0	D	0.771	deleterious	D	0.656432613	None	None	N
G/Y	0.9623	likely_pathogenic	0.9776	pathogenic	-0.72	Destabilizing	1.0	D	0.757	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.