TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15543	46852;46853;46854	chr2:178619690;178619689;178619688	chr2:179484417;179484416;179484415
N2AB	13902	41929;41930;41931	chr2:178619690;178619689;178619688	chr2:179484417;179484416;179484415
N2A	12975	39148;39149;39150	chr2:178619690;178619689;178619688	chr2:179484417;179484416;179484415
N2B	6478	19657;19658;19659	chr2:178619690;178619689;178619688	chr2:179484417;179484416;179484415
Novex-1	6603	20032;20033;20034	chr2:178619690;178619689;178619688	chr2:179484417;179484416;179484415
Novex-2	6670	20233;20234;20235	chr2:178619690;178619689;178619688	chr2:179484417;179484416;179484415
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Ig-107
• Domain position: 64
• Structural Position: 146
• Q(SASA): 0.5274
• 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	None	None	1.0	D	0.686	0.547	0.557405679382	gnomAD-4.0.0	1.59436E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86441E-06	0	0
P/T	None	None	0.999	D	0.651	0.502	0.584148673918	gnomAD-4.0.0	1.59436E-06	None	None	None	None	N	None	0	0	None	0	2.78056E-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
P/A	0.1695	likely_benign	0.1776	benign	-0.842	Destabilizing	0.998	D	0.563	neutral	D	0.589519459	None	None	N
P/C	0.8964	likely_pathogenic	0.9062	pathogenic	-0.557	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
P/D	0.8077	likely_pathogenic	0.7821	pathogenic	-0.962	Destabilizing	1.0	D	0.673	neutral	None	None	None	None	N
P/E	0.5682	likely_pathogenic	0.5426	ambiguous	-1.038	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
P/F	0.8233	likely_pathogenic	0.8263	pathogenic	-0.891	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
P/G	0.613	likely_pathogenic	0.5917	pathogenic	-1.038	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
P/H	0.5327	ambiguous	0.5368	ambiguous	-0.623	Destabilizing	1.0	D	0.684	prob.neutral	D	0.587152048	None	None	N
P/I	0.6132	likely_pathogenic	0.6058	pathogenic	-0.441	Destabilizing	0.998	D	0.721	prob.delet.	None	None	None	None	N
P/K	0.6585	likely_pathogenic	0.6242	pathogenic	-0.85	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
P/L	0.2945	likely_benign	0.292	benign	-0.441	Destabilizing	0.64	D	0.478	neutral	D	0.528904415	None	None	N
P/M	0.6099	likely_pathogenic	0.6013	pathogenic	-0.396	Destabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	N
P/N	0.7081	likely_pathogenic	0.6879	pathogenic	-0.507	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
P/Q	0.371	ambiguous	0.3563	ambiguous	-0.744	Destabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	N
P/R	0.4807	ambiguous	0.4565	ambiguous	-0.276	Destabilizing	1.0	D	0.727	prob.delet.	D	0.549329816	None	None	N
P/S	0.3425	ambiguous	0.3505	ambiguous	-0.823	Destabilizing	1.0	D	0.686	prob.neutral	D	0.548148029	None	None	N
P/T	0.3165	likely_benign	0.3225	benign	-0.804	Destabilizing	0.999	D	0.651	neutral	D	0.527927114	None	None	N
P/V	0.4256	ambiguous	0.4249	ambiguous	-0.54	Destabilizing	0.998	D	0.625	neutral	None	None	None	None	N
P/W	0.9061	likely_pathogenic	0.8997	pathogenic	-1.02	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	N
P/Y	0.7523	likely_pathogenic	0.7514	pathogenic	-0.742	Destabilizing	1.0	D	0.725	prob.delet.	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.