TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23699	71320;71321;71322	chr2:178575037;178575036;178575035	chr2:179439764;179439763;179439762
N2AB	22058	66397;66398;66399	chr2:178575037;178575036;178575035	chr2:179439764;179439763;179439762
N2A	21131	63616;63617;63618	chr2:178575037;178575036;178575035	chr2:179439764;179439763;179439762
N2B	14634	44125;44126;44127	chr2:178575037;178575036;178575035	chr2:179439764;179439763;179439762
Novex-1	14759	44500;44501;44502	chr2:178575037;178575036;178575035	chr2:179439764;179439763;179439762
Novex-2	14826	44701;44702;44703	chr2:178575037;178575036;178575035	chr2:179439764;179439763;179439762
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-130
• Domain position: 63
• Structural Position: 148
• Q(SASA): 0.5234
• 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/N	None	None	0.001	N	0.128	0.05	0.143124449307	gnomAD-4.0.0	1.3687E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.31422E-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	0.0712	likely_benign	0.0735	benign	-0.254	Destabilizing	0.007	N	0.137	neutral	None	None	None	None	N
S/C	0.1192	likely_benign	0.1256	benign	-0.293	Destabilizing	0.987	D	0.317	neutral	N	0.493652279	None	None	N
S/D	0.2451	likely_benign	0.2537	benign	0.173	Stabilizing	0.39	N	0.2	neutral	None	None	None	None	N
S/E	0.3166	likely_benign	0.325	benign	0.064	Stabilizing	0.209	N	0.202	neutral	None	None	None	None	N
S/F	0.2195	likely_benign	0.2288	benign	-0.97	Destabilizing	0.965	D	0.363	neutral	None	None	None	None	N
S/G	0.0694	likely_benign	0.0695	benign	-0.311	Destabilizing	0.166	N	0.287	neutral	N	0.48989976	None	None	N
S/H	0.2641	likely_benign	0.274	benign	-0.719	Destabilizing	0.901	D	0.317	neutral	None	None	None	None	N
S/I	0.1534	likely_benign	0.1568	benign	-0.236	Destabilizing	0.772	D	0.401	neutral	N	0.475548024	None	None	N
S/K	0.4083	ambiguous	0.4184	ambiguous	-0.342	Destabilizing	0.002	N	0.137	neutral	None	None	None	None	N
S/L	0.0937	likely_benign	0.0976	benign	-0.236	Destabilizing	0.561	D	0.317	neutral	None	None	None	None	N
S/M	0.1595	likely_benign	0.1649	benign	-0.064	Destabilizing	0.965	D	0.318	neutral	None	None	None	None	N
S/N	0.0894	likely_benign	0.0862	benign	-0.094	Destabilizing	0.001	N	0.128	neutral	N	0.497633809	None	None	N
S/P	0.2491	likely_benign	0.2198	benign	-0.217	Destabilizing	0.722	D	0.375	neutral	None	None	None	None	N
S/Q	0.3278	likely_benign	0.3305	benign	-0.34	Destabilizing	0.561	D	0.311	neutral	None	None	None	None	N
S/R	0.402	ambiguous	0.4101	ambiguous	-0.117	Destabilizing	0.326	N	0.296	neutral	N	0.462670781	None	None	N
S/T	0.0713	likely_benign	0.072	benign	-0.226	Destabilizing	0.013	N	0.159	neutral	N	0.485320659	None	None	N
S/V	0.157	likely_benign	0.1601	benign	-0.217	Destabilizing	0.561	D	0.355	neutral	None	None	None	None	N
S/W	0.3074	likely_benign	0.3217	benign	-1.014	Destabilizing	0.991	D	0.415	neutral	None	None	None	None	N
S/Y	0.2107	likely_benign	0.216	benign	-0.711	Destabilizing	0.965	D	0.361	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.