TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19612	59059;59060;59061	chr2:178593374;178593373;178593372	chr2:179458101;179458100;179458099
N2AB	17971	54136;54137;54138	chr2:178593374;178593373;178593372	chr2:179458101;179458100;179458099
N2A	17044	51355;51356;51357	chr2:178593374;178593373;178593372	chr2:179458101;179458100;179458099
N2B	10547	31864;31865;31866	chr2:178593374;178593373;178593372	chr2:179458101;179458100;179458099
Novex-1	10672	32239;32240;32241	chr2:178593374;178593373;178593372	chr2:179458101;179458100;179458099
Novex-2	10739	32440;32441;32442	chr2:178593374;178593373;178593372	chr2:179458101;179458100;179458099
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-30
• Domain position: 34
• Structural Position: 37
• Q(SASA): 0.0947
• 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
N/I	None	None	0.272	N	0.797	0.243	0.436886369515	gnomAD-4.0.0	1.5921E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85958E-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
N/A	0.348	ambiguous	0.3471	ambiguous	-0.965	Destabilizing	None	N	0.564	neutral	None	None	None	None	N
N/C	0.3019	likely_benign	0.3194	benign	-0.212	Destabilizing	0.883	D	0.755	deleterious	None	None	None	None	N
N/D	0.3153	likely_benign	0.3106	benign	-1.287	Destabilizing	0.175	N	0.491	neutral	D	0.52407941	None	None	N
N/E	0.7074	likely_pathogenic	0.736	pathogenic	-1.084	Destabilizing	0.22	N	0.562	neutral	None	None	None	None	N
N/F	0.7747	likely_pathogenic	0.7767	pathogenic	-0.351	Destabilizing	0.667	D	0.769	deleterious	None	None	None	None	N
N/G	0.231	likely_benign	0.2352	benign	-1.378	Destabilizing	None	N	0.168	neutral	None	None	None	None	N
N/H	0.145	likely_benign	0.1492	benign	-0.984	Destabilizing	0.602	D	0.626	neutral	N	0.502530701	None	None	N
N/I	0.7242	likely_pathogenic	0.7539	pathogenic	0.133	Stabilizing	0.272	N	0.797	deleterious	N	0.476497346	None	None	N
N/K	0.5194	ambiguous	0.5464	ambiguous	-0.422	Destabilizing	0.096	N	0.579	neutral	N	0.49764217	None	None	N
N/L	0.5682	likely_pathogenic	0.5677	pathogenic	0.133	Stabilizing	0.124	N	0.764	deleterious	None	None	None	None	N
N/M	0.6443	likely_pathogenic	0.65	pathogenic	0.395	Stabilizing	0.667	D	0.723	prob.delet.	None	None	None	None	N
N/P	0.9833	likely_pathogenic	0.9818	pathogenic	-0.204	Destabilizing	0.667	D	0.776	deleterious	None	None	None	None	N
N/Q	0.503	ambiguous	0.5349	ambiguous	-0.891	Destabilizing	0.497	N	0.681	prob.neutral	None	None	None	None	N
N/R	0.4356	ambiguous	0.4503	ambiguous	-0.667	Destabilizing	0.22	N	0.657	neutral	None	None	None	None	N
N/S	0.0996	likely_benign	0.0986	benign	-1.229	Destabilizing	0.001	N	0.171	neutral	N	0.481749997	None	None	N
N/T	0.2801	likely_benign	0.2755	benign	-0.834	Destabilizing	0.001	N	0.191	neutral	N	0.50532029	None	None	N
N/V	0.6317	likely_pathogenic	0.6543	pathogenic	-0.204	Destabilizing	0.124	N	0.768	deleterious	None	None	None	None	N
N/W	0.8793	likely_pathogenic	0.8927	pathogenic	-0.212	Destabilizing	0.958	D	0.761	deleterious	None	None	None	None	N
N/Y	0.289	likely_benign	0.2951	benign	0.072	Stabilizing	0.602	D	0.743	deleterious	N	0.506744442	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.