TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3938	12037;12038;12039	chr2:178741421;178741420;178741419	chr2:179606148;179606147;179606146
N2AB	3621	11086;11087;11088	chr2:178741421;178741420;178741419	chr2:179606148;179606147;179606146
N2A	None	None	chr2:None	chr2:None
N2B	3575	10948;10949;10950	chr2:178741421;178741420;178741419	chr2:179606148;179606147;179606146
Novex-1	3700	11323;11324;11325	chr2:178741421;178741420;178741419	chr2:179606148;179606147;179606146
Novex-2	3767	11524;11525;11526	chr2:178741421;178741420;178741419	chr2:179606148;179606147;179606146
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-28
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.1961
• 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
P/S	rs866702787	None	1.0	D	0.921	0.646	None	gnomAD-4.0.0	9.60257E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.18751E-06	6.07533E-05	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
P/A	0.4718	ambiguous	0.4541	ambiguous	-1.718	Destabilizing	1.0	D	0.846	deleterious	D	0.716504094	None	None	N
P/C	0.9441	likely_pathogenic	0.9342	pathogenic	-1.413	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
P/D	0.996	likely_pathogenic	0.9943	pathogenic	-1.85	Destabilizing	1.0	D	0.925	deleterious	None	None	None	None	N
P/E	0.9843	likely_pathogenic	0.979	pathogenic	-1.835	Destabilizing	1.0	D	0.922	deleterious	None	None	None	None	N
P/F	0.9927	likely_pathogenic	0.9897	pathogenic	-1.384	Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
P/G	0.9619	likely_pathogenic	0.9498	pathogenic	-2.04	Highly Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	N
P/H	0.9801	likely_pathogenic	0.9684	pathogenic	-1.496	Destabilizing	1.0	D	0.881	deleterious	D	0.798624869	None	None	N
P/I	0.9146	likely_pathogenic	0.9028	pathogenic	-0.918	Destabilizing	1.0	D	0.906	deleterious	None	None	None	None	N
P/K	0.9885	likely_pathogenic	0.9846	pathogenic	-1.321	Destabilizing	1.0	D	0.921	deleterious	None	None	None	None	N
P/L	0.8165	likely_pathogenic	0.7544	pathogenic	-0.918	Destabilizing	1.0	D	0.915	deleterious	D	0.764204123	None	None	N
P/M	0.9751	likely_pathogenic	0.9651	pathogenic	-0.836	Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
P/N	0.9916	likely_pathogenic	0.988	pathogenic	-1.213	Destabilizing	1.0	D	0.916	deleterious	None	None	None	None	N
P/Q	0.9635	likely_pathogenic	0.9471	pathogenic	-1.418	Destabilizing	1.0	D	0.915	deleterious	None	None	None	None	N
P/R	0.9614	likely_pathogenic	0.9467	pathogenic	-0.812	Destabilizing	1.0	D	0.919	deleterious	D	0.798624869	None	None	N
P/S	0.8685	likely_pathogenic	0.8366	pathogenic	-1.756	Destabilizing	1.0	D	0.921	deleterious	D	0.764499675	None	None	N
P/T	0.8471	likely_pathogenic	0.8063	pathogenic	-1.634	Destabilizing	1.0	D	0.922	deleterious	D	0.799148673	None	None	N
P/V	0.8184	likely_pathogenic	0.7997	pathogenic	-1.152	Destabilizing	1.0	D	0.921	deleterious	None	None	None	None	N
P/W	0.9979	likely_pathogenic	0.9968	pathogenic	-1.545	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
P/Y	0.9942	likely_pathogenic	0.9913	pathogenic	-1.252	Destabilizing	1.0	D	0.919	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.