TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7310	22153;22154;22155	chr2:178723079;178723078;178723077	chr2:179587806;179587805;179587804
N2AB	6993	21202;21203;21204	chr2:178723079;178723078;178723077	chr2:179587806;179587805;179587804
N2A	6066	18421;18422;18423	chr2:178723079;178723078;178723077	chr2:179587806;179587805;179587804
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: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Ig-57
• Domain position: 81
• Structural Position: 165
• Q(SASA): 0.6265
• 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
R/M	None	None	0.56	N	0.457	0.159	0.259761712551	gnomAD-4.0.0	1.59175E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.8592E-06	0	0
R/S	None	None	0.001	N	0.231	0.096	0.101711395817	gnomAD-4.0.0	1.59178E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85923E-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
R/A	0.1665	likely_benign	0.1986	benign	0.038	Stabilizing	0.016	N	0.351	neutral	None	None	None	None	I
R/C	0.1554	likely_benign	0.1777	benign	-0.08	Destabilizing	0.864	D	0.485	neutral	None	None	None	None	I
R/D	0.3742	ambiguous	0.4473	ambiguous	-0.121	Destabilizing	0.016	N	0.476	neutral	None	None	None	None	I
R/E	0.1697	likely_benign	0.1977	benign	-0.055	Destabilizing	None	N	0.168	neutral	None	None	None	None	I
R/F	0.3213	likely_benign	0.3638	ambiguous	-0.131	Destabilizing	0.12	N	0.521	neutral	None	None	None	None	I
R/G	0.0989	likely_benign	0.1253	benign	-0.166	Destabilizing	0.012	N	0.5	neutral	D	0.52366927	None	None	I
R/H	0.0877	likely_benign	0.0886	benign	-0.644	Destabilizing	None	N	0.177	neutral	None	None	None	None	I
R/I	0.1568	likely_benign	0.1799	benign	0.541	Stabilizing	0.356	N	0.523	neutral	None	None	None	None	I
R/K	0.0645	likely_benign	0.0684	benign	-0.044	Destabilizing	None	N	0.153	neutral	N	0.424771712	None	None	I
R/L	0.1552	likely_benign	0.1772	benign	0.541	Stabilizing	0.031	N	0.475	neutral	None	None	None	None	I
R/M	0.1438	likely_benign	0.1638	benign	0.094	Stabilizing	0.56	D	0.457	neutral	N	0.501293842	None	None	I
R/N	0.2662	likely_benign	0.3114	benign	0.213	Stabilizing	0.016	N	0.364	neutral	None	None	None	None	I
R/P	0.6654	likely_pathogenic	0.6822	pathogenic	0.394	Stabilizing	0.136	N	0.544	neutral	None	None	None	None	I
R/Q	0.0785	likely_benign	0.0835	benign	0.109	Stabilizing	None	N	0.169	neutral	None	None	None	None	I
R/S	0.1822	likely_benign	0.2177	benign	-0.114	Destabilizing	0.001	N	0.231	neutral	N	0.406746099	None	None	I
R/T	0.1014	likely_benign	0.1127	benign	0.085	Stabilizing	0.012	N	0.435	neutral	N	0.438762516	None	None	I
R/V	0.1916	likely_benign	0.2241	benign	0.394	Stabilizing	0.072	N	0.569	neutral	None	None	None	None	I
R/W	0.1307	likely_benign	0.1362	benign	-0.174	Destabilizing	None	N	0.321	neutral	N	0.493721407	None	None	I
R/Y	0.2548	likely_benign	0.2849	benign	0.225	Stabilizing	0.038	N	0.567	neutral	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.