TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21580	64963;64964;64965	chr2:178584903;178584902;178584901	chr2:179449630;179449629;179449628
N2AB	19939	60040;60041;60042	chr2:178584903;178584902;178584901	chr2:179449630;179449629;179449628
N2A	19012	57259;57260;57261	chr2:178584903;178584902;178584901	chr2:179449630;179449629;179449628
N2B	12515	37768;37769;37770	chr2:178584903;178584902;178584901	chr2:179449630;179449629;179449628
Novex-1	12640	38143;38144;38145	chr2:178584903;178584902;178584901	chr2:179449630;179449629;179449628
Novex-2	12707	38344;38345;38346	chr2:178584903;178584902;178584901	chr2:179449630;179449629;179449628
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: Fn3-44
• Domain position: 22
• Structural Position: 23
• Q(SASA): 0.2925
• 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	0.002	N	0.359	0.244	0.585930602222	gnomAD-4.0.0	6.84394E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.65706E-05

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	0.0846	likely_benign	0.0797	benign	-0.766	Destabilizing	0.002	N	0.138	neutral	D	0.524372985	None	None	N
S/C	0.1241	likely_benign	0.1166	benign	-0.515	Destabilizing	0.92	D	0.542	neutral	None	None	None	None	N
S/D	0.4879	ambiguous	0.4859	ambiguous	-1.166	Destabilizing	0.766	D	0.474	neutral	None	None	None	None	N
S/E	0.4981	ambiguous	0.5207	ambiguous	-0.984	Destabilizing	0.617	D	0.399	neutral	None	None	None	None	N
S/F	0.1919	likely_benign	0.1697	benign	-0.723	Destabilizing	0.85	D	0.587	neutral	None	None	None	None	N
S/G	0.1578	likely_benign	0.1455	benign	-1.162	Destabilizing	0.25	N	0.384	neutral	None	None	None	None	N
S/H	0.2574	likely_benign	0.274	benign	-1.585	Destabilizing	0.992	D	0.527	neutral	None	None	None	None	N
S/I	0.1906	likely_benign	0.1791	benign	0.237	Stabilizing	0.005	N	0.417	neutral	None	None	None	None	N
S/K	0.5579	ambiguous	0.5832	pathogenic	-0.129	Destabilizing	0.617	D	0.398	neutral	None	None	None	None	N
S/L	0.1102	likely_benign	0.0981	benign	0.237	Stabilizing	0.002	N	0.359	neutral	N	0.472617141	None	None	N
S/M	0.1922	likely_benign	0.1772	benign	0.216	Stabilizing	0.85	D	0.532	neutral	None	None	None	None	N
S/N	0.1812	likely_benign	0.1667	benign	-0.8	Destabilizing	0.766	D	0.488	neutral	None	None	None	None	N
S/P	0.9713	likely_pathogenic	0.97	pathogenic	-0.062	Destabilizing	0.896	D	0.548	neutral	D	0.542187005	None	None	N
S/Q	0.3694	ambiguous	0.3901	ambiguous	-0.58	Destabilizing	0.92	D	0.518	neutral	None	None	None	None	N
S/R	0.4738	ambiguous	0.5024	ambiguous	-0.523	Destabilizing	0.85	D	0.549	neutral	None	None	None	None	N
S/T	0.0801	likely_benign	0.0773	benign	-0.501	Destabilizing	0.334	N	0.394	neutral	N	0.493183286	None	None	N
S/V	0.1827	likely_benign	0.177	benign	-0.062	Destabilizing	0.103	N	0.453	neutral	None	None	None	None	N
S/W	0.3801	ambiguous	0.3801	ambiguous	-0.952	Destabilizing	0.992	D	0.647	neutral	None	None	None	None	N
S/Y	0.1911	likely_benign	0.1832	benign	-0.495	Destabilizing	0.92	D	0.574	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.