TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6087	18484;18485;18486	chr2:178730141;178730140;178730139	chr2:179594868;179594867;179594866
N2AB	5770	17533;17534;17535	chr2:178730141;178730140;178730139	chr2:179594868;179594867;179594866
N2A	4843	14752;14753;14754	chr2:178730141;178730140;178730139	chr2:179594868;179594867;179594866
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: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-44
• Domain position: 76
• Structural Position: 159
• Q(SASA): 0.2428
• 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/N	rs1270956493	None	0.684	N	0.429	0.283	0.270001397563	gnomAD-3.1.2	6.59E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
S/N	rs1270956493	None	0.684	N	0.429	0.283	0.270001397563	gnomAD-4.0.0	6.59457E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47258E-05	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	0.1046	likely_benign	0.0967	benign	-0.573	Destabilizing	0.016	N	0.114	neutral	None	None	None	None	N
S/C	0.1861	likely_benign	0.1549	benign	-0.667	Destabilizing	0.994	D	0.5	neutral	D	0.522474405	None	None	N
S/D	0.5099	ambiguous	0.5584	ambiguous	-1.214	Destabilizing	0.742	D	0.407	neutral	None	None	None	None	N
S/E	0.5637	ambiguous	0.5602	ambiguous	-1.21	Destabilizing	0.373	N	0.38	neutral	None	None	None	None	N
S/F	0.228	likely_benign	0.213	benign	-0.861	Destabilizing	0.953	D	0.621	neutral	None	None	None	None	N
S/G	0.1352	likely_benign	0.1499	benign	-0.805	Destabilizing	0.472	N	0.377	neutral	N	0.485999179	None	None	N
S/H	0.2868	likely_benign	0.3233	benign	-1.335	Destabilizing	0.953	D	0.521	neutral	None	None	None	None	N
S/I	0.1715	likely_benign	0.1807	benign	-0.061	Destabilizing	0.884	D	0.611	neutral	N	0.503863171	None	None	N
S/K	0.6549	likely_pathogenic	0.6733	pathogenic	-0.791	Destabilizing	0.373	N	0.379	neutral	None	None	None	None	N
S/L	0.1337	likely_benign	0.1245	benign	-0.061	Destabilizing	0.59	D	0.589	neutral	None	None	None	None	N
S/M	0.2073	likely_benign	0.2029	benign	0.276	Stabilizing	0.953	D	0.521	neutral	None	None	None	None	N
S/N	0.1306	likely_benign	0.1606	benign	-0.947	Destabilizing	0.684	D	0.429	neutral	N	0.501292277	None	None	N
S/P	0.9484	likely_pathogenic	0.9682	pathogenic	-0.199	Destabilizing	0.854	D	0.513	neutral	None	None	None	None	N
S/Q	0.4233	ambiguous	0.4436	ambiguous	-1.191	Destabilizing	0.101	N	0.119	neutral	None	None	None	None	N
S/R	0.5376	ambiguous	0.5731	pathogenic	-0.585	Destabilizing	0.028	N	0.323	neutral	N	0.48333938	None	None	N
S/T	0.0685	likely_benign	0.0684	benign	-0.823	Destabilizing	0.007	N	0.139	neutral	N	0.505350081	None	None	N
S/V	0.1895	likely_benign	0.188	benign	-0.199	Destabilizing	0.59	D	0.61	neutral	None	None	None	None	N
S/W	0.3853	ambiguous	0.4082	ambiguous	-0.899	Destabilizing	0.996	D	0.642	neutral	None	None	None	None	N
S/Y	0.2249	likely_benign	0.2248	benign	-0.578	Destabilizing	0.984	D	0.627	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.