TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8628	26107;26108;26109	chr2:178715532;178715531;178715530	chr2:179580259;179580258;179580257
N2AB	8311	25156;25157;25158	chr2:178715532;178715531;178715530	chr2:179580259;179580258;179580257
N2A	7384	22375;22376;22377	chr2:178715532;178715531;178715530	chr2:179580259;179580258;179580257
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: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-71
• Domain position: 80
• Structural Position: 163
• Q(SASA): 0.6282
• 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
A/V	None	None	0.682	N	0.495	0.25	0.434272847907	gnomAD-4.0.0	1.59257E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86157E-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
A/C	0.6656	likely_pathogenic	0.6295	pathogenic	-0.821	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
A/D	0.7197	likely_pathogenic	0.7382	pathogenic	-0.511	Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	I
A/E	0.5924	likely_pathogenic	0.5928	pathogenic	-0.665	Destabilizing	0.999	D	0.7	prob.neutral	N	0.514765404	None	None	I
A/F	0.3324	likely_benign	0.3416	ambiguous	-0.915	Destabilizing	0.999	D	0.759	deleterious	None	None	None	None	I
A/G	0.2879	likely_benign	0.2709	benign	-0.215	Destabilizing	0.967	D	0.648	neutral	N	0.507243759	None	None	I
A/H	0.6773	likely_pathogenic	0.6753	pathogenic	-0.216	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	I
A/I	0.256	likely_benign	0.2481	benign	-0.4	Destabilizing	0.992	D	0.639	neutral	None	None	None	None	I
A/K	0.7346	likely_pathogenic	0.7126	pathogenic	-0.526	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
A/L	0.2878	likely_benign	0.2866	benign	-0.4	Destabilizing	0.992	D	0.581	neutral	None	None	None	None	I
A/M	0.3063	likely_benign	0.3062	benign	-0.524	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	I
A/N	0.577	likely_pathogenic	0.5823	pathogenic	-0.23	Destabilizing	0.994	D	0.757	deleterious	None	None	None	None	I
A/P	0.8705	likely_pathogenic	0.8557	pathogenic	-0.312	Destabilizing	0.999	D	0.706	prob.neutral	D	0.554861481	None	None	I
A/Q	0.5878	likely_pathogenic	0.5727	pathogenic	-0.5	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
A/R	0.6219	likely_pathogenic	0.5929	pathogenic	-0.09	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
A/S	0.1333	likely_benign	0.1357	benign	-0.412	Destabilizing	0.881	D	0.648	neutral	N	0.50673678	None	None	I
A/T	0.1497	likely_benign	0.1484	benign	-0.494	Destabilizing	0.97	D	0.671	neutral	D	0.540209812	None	None	I
A/V	0.1072	likely_benign	0.1049	benign	-0.312	Destabilizing	0.682	D	0.495	neutral	N	0.495578591	None	None	I
A/W	0.834	likely_pathogenic	0.8346	pathogenic	-1.017	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
A/Y	0.6123	likely_pathogenic	0.6033	pathogenic	-0.696	Destabilizing	1.0	D	0.759	deleterious	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.