TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28621	86086;86087;86088	chr2:178560271;178560270;178560269	chr2:179424998;179424997;179424996
N2AB	26980	81163;81164;81165	chr2:178560271;178560270;178560269	chr2:179424998;179424997;179424996
N2A	26053	78382;78383;78384	chr2:178560271;178560270;178560269	chr2:179424998;179424997;179424996
N2B	19556	58891;58892;58893	chr2:178560271;178560270;178560269	chr2:179424998;179424997;179424996
Novex-1	19681	59266;59267;59268	chr2:178560271;178560270;178560269	chr2:179424998;179424997;179424996
Novex-2	19748	59467;59468;59469	chr2:178560271;178560270;178560269	chr2:179424998;179424997;179424996
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-96
• Domain position: 72
• Structural Position: 104
• Q(SASA): 0.0899
• 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	rs751308383	-2.82	1.0	D	0.845	0.848	0.853231469175	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.66E-05	0
Y/H	rs751308383	-2.82	1.0	D	0.845	0.848	0.853231469175	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
Y/H	rs751308383	-2.82	1.0	D	0.845	0.848	0.853231469175	gnomAD-4.0.0	1.36331E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.86472E-05	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	0.9891	likely_pathogenic	0.9802	pathogenic	-3.459	Highly Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
Y/C	0.9172	likely_pathogenic	0.8555	pathogenic	-1.925	Destabilizing	1.0	D	0.871	deleterious	D	0.669453425	None	None	N
Y/D	0.9867	likely_pathogenic	0.9793	pathogenic	-3.648	Highly Destabilizing	1.0	D	0.873	deleterious	D	0.694759372	None	None	N
Y/E	0.9956	likely_pathogenic	0.9926	pathogenic	-3.484	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
Y/F	0.33	likely_benign	0.3114	benign	-1.441	Destabilizing	0.999	D	0.763	deleterious	D	0.617257457	None	None	N
Y/G	0.9735	likely_pathogenic	0.9581	pathogenic	-3.821	Highly Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
Y/H	0.9712	likely_pathogenic	0.9519	pathogenic	-2.226	Highly Destabilizing	1.0	D	0.845	deleterious	D	0.694759372	None	None	N
Y/I	0.9367	likely_pathogenic	0.8994	pathogenic	-2.243	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
Y/K	0.9971	likely_pathogenic	0.9956	pathogenic	-2.445	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
Y/L	0.9097	likely_pathogenic	0.873	pathogenic	-2.243	Highly Destabilizing	0.999	D	0.828	deleterious	None	None	None	None	N
Y/M	0.9531	likely_pathogenic	0.9303	pathogenic	-1.798	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
Y/N	0.9347	likely_pathogenic	0.8973	pathogenic	-3.094	Highly Destabilizing	1.0	D	0.875	deleterious	D	0.694557568	None	None	N
Y/P	0.999	likely_pathogenic	0.9984	pathogenic	-2.663	Highly Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
Y/Q	0.9959	likely_pathogenic	0.9927	pathogenic	-2.96	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
Y/R	0.9931	likely_pathogenic	0.9894	pathogenic	-1.945	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
Y/S	0.9745	likely_pathogenic	0.9587	pathogenic	-3.428	Highly Destabilizing	1.0	D	0.895	deleterious	D	0.694759372	None	None	N
Y/T	0.9844	likely_pathogenic	0.9716	pathogenic	-3.169	Highly Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
Y/V	0.8738	likely_pathogenic	0.8175	pathogenic	-2.663	Highly Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
Y/W	0.8598	likely_pathogenic	0.8333	pathogenic	-0.82	Destabilizing	1.0	D	0.822	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.