TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9543	28852;28853;28854	chr2:178709692;178709691;178709690	chr2:179574419;179574418;179574417
N2AB	9226	27901;27902;27903	chr2:178709692;178709691;178709690	chr2:179574419;179574418;179574417
N2A	8299	25120;25121;25122	chr2:178709692;178709691;178709690	chr2:179574419;179574418;179574417
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: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-81
• Domain position: 51
• Structural Position: 125
• Q(SASA): 0.3828
• 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	rs752853962	0.255	0.062	None	0.37	0.097	0.402326594622	gnomAD-2.1.1	8.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.77E-05	0
T/I	rs752853962	0.255	0.062	None	0.37	0.097	0.402326594622	gnomAD-4.0.0	4.10506E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.39665E-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	0.0782	likely_benign	0.0782	benign	-0.53	Destabilizing	0.027	N	0.334	neutral	None	None	None	None	N
T/C	0.3473	ambiguous	0.3606	ambiguous	-0.412	Destabilizing	0.824	D	0.411	neutral	None	None	None	None	N
T/D	0.3123	likely_benign	0.2982	benign	-0.031	Destabilizing	0.149	N	0.381	neutral	None	None	None	None	N
T/E	0.3001	likely_benign	0.3006	benign	-0.018	Destabilizing	0.081	N	0.333	neutral	None	None	None	None	N
T/F	0.1663	likely_benign	0.1624	benign	-0.561	Destabilizing	0.38	N	0.521	neutral	None	None	None	None	N
T/G	0.2158	likely_benign	0.217	benign	-0.794	Destabilizing	0.081	N	0.414	neutral	None	None	None	None	N
T/H	0.1909	likely_benign	0.1921	benign	-1.046	Destabilizing	0.824	D	0.475	neutral	None	None	None	None	N
T/I	0.1143	likely_benign	0.1036	benign	0.079	Stabilizing	0.062	N	0.37	neutral	None	None	None	None	N
T/K	0.2255	likely_benign	0.2288	benign	-0.651	Destabilizing	0.062	N	0.327	neutral	None	None	None	None	N
T/L	0.087	likely_benign	0.0852	benign	0.079	Stabilizing	0.012	N	0.355	neutral	None	None	None	None	N
T/M	0.0895	likely_benign	0.0957	benign	0.076	Stabilizing	0.005	N	0.375	neutral	None	None	None	None	N
T/N	0.1043	likely_benign	0.1025	benign	-0.597	Destabilizing	0.081	N	0.357	neutral	None	None	None	None	N
T/P	0.5191	ambiguous	0.5126	ambiguous	-0.09	Destabilizing	0.484	N	0.416	neutral	None	None	None	None	N
T/Q	0.2184	likely_benign	0.2325	benign	-0.66	Destabilizing	0.38	N	0.427	neutral	None	None	None	None	N
T/R	0.1815	likely_benign	0.1833	benign	-0.492	Destabilizing	0.317	N	0.418	neutral	None	None	None	None	N
T/S	0.0827	likely_benign	0.0833	benign	-0.83	Destabilizing	None	N	0.125	neutral	None	None	None	None	N
T/V	0.1134	likely_benign	0.1075	benign	-0.09	Destabilizing	0.081	N	0.323	neutral	None	None	None	None	N
T/W	0.5106	ambiguous	0.5181	ambiguous	-0.588	Destabilizing	0.935	D	0.528	neutral	None	None	None	None	N
T/Y	0.2161	likely_benign	0.2216	benign	-0.325	Destabilizing	0.555	D	0.51	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.