TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29782	89569;89570;89571	chr2:178553661;178553660;178553659	chr2:179418388;179418387;179418386
N2AB	28141	84646;84647;84648	chr2:178553661;178553660;178553659	chr2:179418388;179418387;179418386
N2A	27214	81865;81866;81867	chr2:178553661;178553660;178553659	chr2:179418388;179418387;179418386
N2B	20717	62374;62375;62376	chr2:178553661;178553660;178553659	chr2:179418388;179418387;179418386
Novex-1	20842	62749;62750;62751	chr2:178553661;178553660;178553659	chr2:179418388;179418387;179418386
Novex-2	20909	62950;62951;62952	chr2:178553661;178553660;178553659	chr2:179418388;179418387;179418386
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-105
• Domain position: 49
• Structural Position: 66
• Q(SASA): 0.4567
• 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
T/I	rs1400626224	None	0.001	N	0.176	0.101	0.209622950755	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/I	rs1400626224	None	0.001	N	0.176	0.101	0.209622950755	gnomAD-4.0.0	6.57281E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.46998E-05	0	0
T/S	None	None	0.09	N	0.301	0.077	0.104622674875	gnomAD-4.0.0	1.59114E-06	None	None	None	None	N	None	0	2.28634E-05	None	0	0	None	0	0	0	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
T/A	0.076	likely_benign	0.0727	benign	-0.643	Destabilizing	0.001	N	0.071	neutral	N	0.484424943	None	None	N
T/C	0.2718	likely_benign	0.2597	benign	-0.452	Destabilizing	0.944	D	0.333	neutral	None	None	None	None	N
T/D	0.2629	likely_benign	0.2331	benign	0.242	Stabilizing	0.563	D	0.356	neutral	None	None	None	None	N
T/E	0.1519	likely_benign	0.1436	benign	0.219	Stabilizing	0.388	N	0.29	neutral	None	None	None	None	N
T/F	0.168	likely_benign	0.1616	benign	-0.823	Destabilizing	0.69	D	0.386	neutral	None	None	None	None	N
T/G	0.1863	likely_benign	0.1829	benign	-0.86	Destabilizing	0.241	N	0.285	neutral	None	None	None	None	N
T/H	0.1535	likely_benign	0.1519	benign	-1.04	Destabilizing	0.981	D	0.352	neutral	None	None	None	None	N
T/I	0.0968	likely_benign	0.0874	benign	-0.173	Destabilizing	0.001	N	0.176	neutral	N	0.464204387	None	None	N
T/K	0.1033	likely_benign	0.1025	benign	-0.536	Destabilizing	0.241	N	0.275	neutral	None	None	None	None	N
T/L	0.0759	likely_benign	0.0711	benign	-0.173	Destabilizing	0.043	N	0.303	neutral	None	None	None	None	N
T/M	0.0809	likely_benign	0.0746	benign	-0.073	Destabilizing	0.69	D	0.337	neutral	None	None	None	None	N
T/N	0.0873	likely_benign	0.0849	benign	-0.421	Destabilizing	0.773	D	0.328	neutral	N	0.474842668	None	None	N
T/P	0.3817	ambiguous	0.3595	ambiguous	-0.298	Destabilizing	0.773	D	0.361	neutral	N	0.475661199	None	None	N
T/Q	0.1287	likely_benign	0.1291	benign	-0.575	Destabilizing	0.69	D	0.372	neutral	None	None	None	None	N
T/R	0.1042	likely_benign	0.102	benign	-0.278	Destabilizing	0.002	N	0.172	neutral	None	None	None	None	N
T/S	0.0986	likely_benign	0.0961	benign	-0.725	Destabilizing	0.09	N	0.301	neutral	N	0.470668999	None	None	N
T/V	0.0826	likely_benign	0.078	benign	-0.298	Destabilizing	0.043	N	0.279	neutral	None	None	None	None	N
T/W	0.46	ambiguous	0.451	ambiguous	-0.769	Destabilizing	0.981	D	0.417	neutral	None	None	None	None	N
T/Y	0.1778	likely_benign	0.1795	benign	-0.526	Destabilizing	0.818	D	0.371	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.