TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31953	96082;96083;96084	chr2:178544372;178544371;178544370	chr2:179409099;179409098;179409097
N2AB	30312	91159;91160;91161	chr2:178544372;178544371;178544370	chr2:179409099;179409098;179409097
N2A	29385	88378;88379;88380	chr2:178544372;178544371;178544370	chr2:179409099;179409098;179409097
N2B	22888	68887;68888;68889	chr2:178544372;178544371;178544370	chr2:179409099;179409098;179409097
Novex-1	23013	69262;69263;69264	chr2:178544372;178544371;178544370	chr2:179409099;179409098;179409097
Novex-2	23080	69463;69464;69465	chr2:178544372;178544371;178544370	chr2:179409099;179409098;179409097
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: Fn3-121
• Domain position: 45
• Structural Position: 60
• Q(SASA): 0.2468
• 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/S	None	None	0.103	N	0.163	0.047	0.104622674875	gnomAD-4.0.0	1.59137E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85869E-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	0.0837	likely_benign	0.0797	benign	-0.433	Destabilizing	0.026	N	0.209	neutral	N	0.442132817	None	None	N
T/C	0.3181	likely_benign	0.3134	benign	-0.2	Destabilizing	0.999	D	0.421	neutral	None	None	None	None	N
T/D	0.2839	likely_benign	0.2704	benign	-0.224	Destabilizing	0.976	D	0.382	neutral	None	None	None	None	N
T/E	0.2621	likely_benign	0.2392	benign	-0.288	Destabilizing	0.919	D	0.347	neutral	None	None	None	None	N
T/F	0.3131	likely_benign	0.2974	benign	-0.757	Destabilizing	0.996	D	0.503	neutral	None	None	None	None	N
T/G	0.1608	likely_benign	0.1501	benign	-0.608	Destabilizing	0.851	D	0.359	neutral	None	None	None	None	N
T/H	0.2594	likely_benign	0.2422	benign	-0.944	Destabilizing	0.999	D	0.524	neutral	None	None	None	None	N
T/I	0.2369	likely_benign	0.2226	benign	-0.078	Destabilizing	0.968	D	0.384	neutral	N	0.474985955	None	None	N
T/K	0.1645	likely_benign	0.1531	benign	-0.594	Destabilizing	0.919	D	0.379	neutral	None	None	None	None	N
T/L	0.137	likely_benign	0.1291	benign	-0.078	Destabilizing	0.919	D	0.323	neutral	None	None	None	None	N
T/M	0.1159	likely_benign	0.1087	benign	0.216	Stabilizing	0.999	D	0.393	neutral	None	None	None	None	N
T/N	0.1086	likely_benign	0.1046	benign	-0.331	Destabilizing	0.968	D	0.357	neutral	N	0.453213815	None	None	N
T/P	0.3384	likely_benign	0.3032	benign	-0.166	Destabilizing	0.984	D	0.387	neutral	N	0.475610672	None	None	N
T/Q	0.2184	likely_benign	0.2057	benign	-0.593	Destabilizing	0.988	D	0.373	neutral	None	None	None	None	N
T/R	0.1555	likely_benign	0.1438	benign	-0.264	Destabilizing	0.976	D	0.382	neutral	None	None	None	None	N
T/S	0.0836	likely_benign	0.081	benign	-0.511	Destabilizing	0.103	N	0.163	neutral	N	0.404361075	None	None	N
T/V	0.173	likely_benign	0.1679	benign	-0.166	Destabilizing	0.851	D	0.304	neutral	None	None	None	None	N
T/W	0.598	likely_pathogenic	0.5752	pathogenic	-0.743	Destabilizing	0.999	D	0.61	neutral	None	None	None	None	N
T/Y	0.3127	likely_benign	0.2969	benign	-0.499	Destabilizing	0.996	D	0.502	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.