TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24105	72538;72539;72540	chr2:178573819;178573818;178573817	chr2:179438546;179438545;179438544
N2AB	22464	67615;67616;67617	chr2:178573819;178573818;178573817	chr2:179438546;179438545;179438544
N2A	21537	64834;64835;64836	chr2:178573819;178573818;178573817	chr2:179438546;179438545;179438544
N2B	15040	45343;45344;45345	chr2:178573819;178573818;178573817	chr2:179438546;179438545;179438544
Novex-1	15165	45718;45719;45720	chr2:178573819;178573818;178573817	chr2:179438546;179438545;179438544
Novex-2	15232	45919;45920;45921	chr2:178573819;178573818;178573817	chr2:179438546;179438545;179438544
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: Ig-131
• Domain position: 77
• Structural Position: 159
• Q(SASA): 0.2997
• 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
T/I	None	None	0.896	N	0.439	0.367	0.481616744073	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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
T/A	0.0695	likely_benign	0.0757	benign	-0.705	Destabilizing	0.099	N	0.252	neutral	N	0.508702604	None	None	I
T/C	0.2869	likely_benign	0.3279	benign	-0.486	Destabilizing	0.992	D	0.44	neutral	None	None	None	None	I
T/D	0.4746	ambiguous	0.5673	pathogenic	-0.774	Destabilizing	0.617	D	0.445	neutral	None	None	None	None	I
T/E	0.2959	likely_benign	0.3487	ambiguous	-0.799	Destabilizing	0.617	D	0.422	neutral	None	None	None	None	I
T/F	0.2071	likely_benign	0.2582	benign	-0.968	Destabilizing	0.92	D	0.564	neutral	None	None	None	None	I
T/G	0.2273	likely_benign	0.2468	benign	-0.924	Destabilizing	0.25	N	0.515	neutral	None	None	None	None	I
T/H	0.2073	likely_benign	0.2227	benign	-1.359	Destabilizing	0.92	D	0.539	neutral	None	None	None	None	I
T/I	0.1334	likely_benign	0.1681	benign	-0.221	Destabilizing	0.896	D	0.439	neutral	N	0.505241012	None	None	I
T/K	0.1309	likely_benign	0.1476	benign	-0.769	Destabilizing	0.447	N	0.444	neutral	None	None	None	None	I
T/L	0.0988	likely_benign	0.1205	benign	-0.221	Destabilizing	0.617	D	0.416	neutral	None	None	None	None	I
T/M	0.091	likely_benign	0.1046	benign	0.217	Stabilizing	0.972	D	0.447	neutral	None	None	None	None	I
T/N	0.1259	likely_benign	0.1491	benign	-0.724	Destabilizing	0.379	N	0.386	neutral	N	0.520978468	None	None	I
T/P	0.713	likely_pathogenic	0.7563	pathogenic	-0.352	Destabilizing	0.712	D	0.436	neutral	N	0.51833703	None	None	I
T/Q	0.1763	likely_benign	0.1878	benign	-1.011	Destabilizing	0.85	D	0.441	neutral	None	None	None	None	I
T/R	0.1102	likely_benign	0.125	benign	-0.469	Destabilizing	0.85	D	0.434	neutral	None	None	None	None	I
T/S	0.0914	likely_benign	0.0986	benign	-0.886	Destabilizing	0.002	N	0.144	neutral	N	0.408789113	None	None	I
T/V	0.1025	likely_benign	0.1257	benign	-0.352	Destabilizing	0.617	D	0.378	neutral	None	None	None	None	I
T/W	0.5277	ambiguous	0.5649	pathogenic	-0.925	Destabilizing	0.992	D	0.587	neutral	None	None	None	None	I
T/Y	0.2371	likely_benign	0.2614	benign	-0.664	Destabilizing	0.972	D	0.551	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.