TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7636	23131;23132;23133	chr2:178721113;178721112;178721111	chr2:179585840;179585839;179585838
N2AB	7319	22180;22181;22182	chr2:178721113;178721112;178721111	chr2:179585840;179585839;179585838
N2A	6392	19399;19400;19401	chr2:178721113;178721112;178721111	chr2:179585840;179585839;179585838
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: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-61
• Domain position: 29
• Structural Position: 42
• Q(SASA): 0.7587
• Predicted PPI site: I

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/A	rs1220583171	-0.024	0.883	D	0.561	0.548	0.449187354989	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
P/A	rs1220583171	-0.024	0.883	D	0.561	0.548	0.449187354989	gnomAD-4.0.0	3.18538E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.72318E-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
P/A	0.3158	likely_benign	0.7026	pathogenic	-0.297	Destabilizing	0.883	D	0.561	neutral	D	0.536109933	None	None	I
P/C	0.9267	likely_pathogenic	0.9821	pathogenic	-0.747	Destabilizing	0.999	D	0.705	prob.neutral	None	None	None	None	I
P/D	0.8069	likely_pathogenic	0.9543	pathogenic	-0.292	Destabilizing	0.944	D	0.647	neutral	None	None	None	None	I
P/E	0.5783	likely_pathogenic	0.8825	pathogenic	-0.413	Destabilizing	0.964	D	0.653	neutral	None	None	None	None	I
P/F	0.9374	likely_pathogenic	0.9885	pathogenic	-0.667	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
P/G	0.7346	likely_pathogenic	0.9189	pathogenic	-0.361	Destabilizing	0.98	D	0.626	neutral	None	None	None	None	I
P/H	0.6427	likely_pathogenic	0.9107	pathogenic	0.019	Stabilizing	1.0	D	0.64	neutral	None	None	None	None	I
P/I	0.8244	likely_pathogenic	0.9401	pathogenic	-0.274	Destabilizing	0.999	D	0.695	prob.neutral	None	None	None	None	I
P/K	0.7545	likely_pathogenic	0.9453	pathogenic	-0.354	Destabilizing	0.999	D	0.652	neutral	None	None	None	None	I
P/L	0.4506	ambiguous	0.7949	pathogenic	-0.274	Destabilizing	0.999	D	0.671	neutral	D	0.612010596	None	None	I
P/M	0.7555	likely_pathogenic	0.9312	pathogenic	-0.512	Destabilizing	1.0	D	0.643	neutral	None	None	None	None	I
P/N	0.7896	likely_pathogenic	0.9498	pathogenic	-0.135	Destabilizing	0.991	D	0.641	neutral	None	None	None	None	I
P/Q	0.4689	ambiguous	0.8397	pathogenic	-0.356	Destabilizing	0.998	D	0.645	neutral	D	0.526728637	None	None	I
P/R	0.5758	likely_pathogenic	0.8812	pathogenic	0.095	Stabilizing	0.999	D	0.661	neutral	D	0.611606988	None	None	I
P/S	0.4502	ambiguous	0.8429	pathogenic	-0.444	Destabilizing	0.823	D	0.337	neutral	D	0.549098853	None	None	I
P/T	0.3712	ambiguous	0.721	pathogenic	-0.473	Destabilizing	0.976	D	0.665	neutral	D	0.611606988	None	None	I
P/V	0.6649	likely_pathogenic	0.8738	pathogenic	-0.252	Destabilizing	0.997	D	0.647	neutral	None	None	None	None	I
P/W	0.9491	likely_pathogenic	0.9902	pathogenic	-0.728	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	I
P/Y	0.9189	likely_pathogenic	0.9845	pathogenic	-0.445	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I

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.