TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19696	59311;59312;59313	chr2:178593033;178593032;178593031	chr2:179457760;179457759;179457758
N2AB	18055	54388;54389;54390	chr2:178593033;178593032;178593031	chr2:179457760;179457759;179457758
N2A	17128	51607;51608;51609	chr2:178593033;178593032;178593031	chr2:179457760;179457759;179457758
N2B	10631	32116;32117;32118	chr2:178593033;178593032;178593031	chr2:179457760;179457759;179457758
Novex-1	10756	32491;32492;32493	chr2:178593033;178593032;178593031	chr2:179457760;179457759;179457758
Novex-2	10823	32692;32693;32694	chr2:178593033;178593032;178593031	chr2:179457760;179457759;179457758
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Fn3-31
• Domain position: 17
• Structural Position: 19
• Q(SASA): 0.1349
• 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
S/L	None	None	1.0	D	0.753	0.506	0.73762428413	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
S/A	0.1613	likely_benign	0.1534	benign	-0.088	Destabilizing	0.997	D	0.47	neutral	N	0.489306272	None	None	N
S/C	0.1913	likely_benign	0.1965	benign	-0.727	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
S/D	0.8793	likely_pathogenic	0.8574	pathogenic	-2.225	Highly Destabilizing	0.999	D	0.527	neutral	None	None	None	None	N
S/E	0.8732	likely_pathogenic	0.8616	pathogenic	-2.155	Highly Destabilizing	0.999	D	0.506	neutral	None	None	None	None	N
S/F	0.5232	ambiguous	0.5434	ambiguous	-0.583	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
S/G	0.2475	likely_benign	0.2306	benign	-0.327	Destabilizing	0.999	D	0.485	neutral	None	None	None	None	N
S/H	0.6386	likely_pathogenic	0.6413	pathogenic	-1.002	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
S/I	0.6359	likely_pathogenic	0.6341	pathogenic	0.443	Stabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
S/K	0.9609	likely_pathogenic	0.9559	pathogenic	-0.472	Destabilizing	0.999	D	0.519	neutral	None	None	None	None	N
S/L	0.3328	likely_benign	0.3168	benign	0.443	Stabilizing	1.0	D	0.753	deleterious	D	0.523010021	None	None	N
S/M	0.3976	ambiguous	0.4042	ambiguous	0.578	Stabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
S/N	0.5094	ambiguous	0.5007	ambiguous	-1.175	Destabilizing	0.999	D	0.524	neutral	None	None	None	None	N
S/P	0.9954	likely_pathogenic	0.9933	pathogenic	0.299	Stabilizing	1.0	D	0.821	deleterious	D	0.538151762	None	None	N
S/Q	0.8267	likely_pathogenic	0.8232	pathogenic	-1.291	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
S/R	0.9266	likely_pathogenic	0.9119	pathogenic	-0.444	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
S/T	0.1064	likely_benign	0.1068	benign	-0.706	Destabilizing	0.999	D	0.483	neutral	N	0.513137271	None	None	N
S/V	0.5378	ambiguous	0.5287	ambiguous	0.299	Stabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
S/W	0.7137	likely_pathogenic	0.7181	pathogenic	-0.913	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
S/Y	0.4601	ambiguous	0.4726	ambiguous	-0.381	Destabilizing	1.0	D	0.869	deleterious	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.