TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7286	22081;22082;22083	chr2:178723151;178723150;178723149	chr2:179587878;179587877;179587876
N2AB	6969	21130;21131;21132	chr2:178723151;178723150;178723149	chr2:179587878;179587877;179587876
N2A	6042	18349;18350;18351	chr2:178723151;178723150;178723149	chr2:179587878;179587877;179587876
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: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-57
• Domain position: 57
• Structural Position: 137
• Q(SASA): 0.2313
• 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
I/V	rs1434099856	None	0.219	N	0.247	0.065	0.420199648628	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
I/V	rs1434099856	None	0.219	N	0.247	0.065	0.420199648628	gnomAD-4.0.0	2.56307E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.56961E-05	0	2.39389E-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
I/A	0.6136	likely_pathogenic	0.727	pathogenic	-2.501	Highly Destabilizing	0.964	D	0.573	neutral	None	None	None	None	N
I/C	0.8277	likely_pathogenic	0.8535	pathogenic	-1.83	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	N
I/D	0.9164	likely_pathogenic	0.9479	pathogenic	-2.741	Highly Destabilizing	0.998	D	0.746	deleterious	None	None	None	None	N
I/E	0.7936	likely_pathogenic	0.8726	pathogenic	-2.562	Highly Destabilizing	0.998	D	0.741	deleterious	None	None	None	None	N
I/F	0.2128	likely_benign	0.2811	benign	-1.514	Destabilizing	0.997	D	0.564	neutral	N	0.501479634	None	None	N
I/G	0.867	likely_pathogenic	0.9168	pathogenic	-3.008	Highly Destabilizing	0.998	D	0.693	prob.neutral	None	None	None	None	N
I/H	0.5837	likely_pathogenic	0.7019	pathogenic	-2.414	Highly Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
I/K	0.487	ambiguous	0.6423	pathogenic	-1.847	Destabilizing	0.998	D	0.746	deleterious	None	None	None	None	N
I/L	0.1636	likely_benign	0.1941	benign	-1.057	Destabilizing	0.817	D	0.458	neutral	N	0.485590651	None	None	N
I/M	0.161	likely_benign	0.1958	benign	-1.019	Destabilizing	0.997	D	0.575	neutral	N	0.496555336	None	None	N
I/N	0.5256	ambiguous	0.6472	pathogenic	-2.06	Highly Destabilizing	0.997	D	0.761	deleterious	N	0.482134384	None	None	N
I/P	0.9833	likely_pathogenic	0.9852	pathogenic	-1.518	Destabilizing	0.999	D	0.765	deleterious	None	None	None	None	N
I/Q	0.573	likely_pathogenic	0.6877	pathogenic	-2.005	Highly Destabilizing	0.999	D	0.781	deleterious	None	None	None	None	N
I/R	0.3296	likely_benign	0.4665	ambiguous	-1.479	Destabilizing	0.998	D	0.775	deleterious	None	None	None	None	N
I/S	0.4786	ambiguous	0.6028	pathogenic	-2.752	Highly Destabilizing	0.961	D	0.64	neutral	N	0.509427749	None	None	N
I/T	0.4309	ambiguous	0.5862	pathogenic	-2.436	Highly Destabilizing	0.4	N	0.421	neutral	N	0.47215744	None	None	N
I/V	0.1212	likely_benign	0.1483	benign	-1.518	Destabilizing	0.219	N	0.247	neutral	N	0.488689904	None	None	N
I/W	0.8298	likely_pathogenic	0.8583	pathogenic	-1.871	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
I/Y	0.5662	likely_pathogenic	0.6219	pathogenic	-1.609	Destabilizing	0.999	D	0.677	prob.neutral	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.