TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30962	93109;93110;93111	chr2:178548742;178548741;178548740	chr2:179413469;179413468;179413467
N2AB	29321	88186;88187;88188	chr2:178548742;178548741;178548740	chr2:179413469;179413468;179413467
N2A	28394	85405;85406;85407	chr2:178548742;178548741;178548740	chr2:179413469;179413468;179413467
N2B	21897	65914;65915;65916	chr2:178548742;178548741;178548740	chr2:179413469;179413468;179413467
Novex-1	22022	66289;66290;66291	chr2:178548742;178548741;178548740	chr2:179413469;179413468;179413467
Novex-2	22089	66490;66491;66492	chr2:178548742;178548741;178548740	chr2:179413469;179413468;179413467
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-150
• Domain position: 36
• Structural Position: 51
• Q(SASA): 0.5946
• 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
P/A	None	None	None	N	0.157	0.06	0.0986583533028	gnomAD-4.0.0	6.84261E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99459E-07	0	0
P/S	None	None	0.166	N	0.361	0.04	0.110078149338	gnomAD-4.0.0	4.10557E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.39675E-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
P/A	0.0728	likely_benign	0.0744	benign	-0.318	Destabilizing	None	N	0.157	neutral	N	0.375054102	None	None	N
P/C	0.4863	ambiguous	0.5077	ambiguous	-0.677	Destabilizing	0.901	D	0.435	neutral	None	None	None	None	N
P/D	0.3352	likely_benign	0.3352	benign	-0.123	Destabilizing	0.722	D	0.438	neutral	None	None	None	None	N
P/E	0.21	likely_benign	0.2136	benign	-0.243	Destabilizing	0.561	D	0.389	neutral	None	None	None	None	N
P/F	0.4535	ambiguous	0.4652	ambiguous	-0.617	Destabilizing	0.901	D	0.505	neutral	None	None	None	None	N
P/G	0.2171	likely_benign	0.2193	benign	-0.415	Destabilizing	0.209	N	0.369	neutral	None	None	None	None	N
P/H	0.2127	likely_benign	0.2164	benign	-0.025	Destabilizing	0.965	D	0.423	neutral	None	None	None	None	N
P/I	0.2469	likely_benign	0.2466	benign	-0.22	Destabilizing	0.007	N	0.234	neutral	None	None	None	None	N
P/K	0.2492	likely_benign	0.2721	benign	-0.304	Destabilizing	0.561	D	0.388	neutral	None	None	None	None	N
P/L	0.1118	likely_benign	0.1123	benign	-0.22	Destabilizing	0.08	N	0.361	neutral	N	0.426386999	None	None	N
P/M	0.2157	likely_benign	0.2198	benign	-0.356	Destabilizing	0.901	D	0.435	neutral	None	None	None	None	N
P/N	0.2294	likely_benign	0.2323	benign	-0.095	Destabilizing	0.722	D	0.493	neutral	None	None	None	None	N
P/Q	0.1403	likely_benign	0.1457	benign	-0.324	Destabilizing	0.873	D	0.437	neutral	N	0.416439364	None	None	N
P/R	0.222	likely_benign	0.2357	benign	0.162	Stabilizing	0.662	D	0.491	neutral	N	0.448589068	None	None	N
P/S	0.1156	likely_benign	0.1161	benign	-0.445	Destabilizing	0.166	N	0.361	neutral	N	0.39706417	None	None	N
P/T	0.0879	likely_benign	0.0869	benign	-0.466	Destabilizing	0.005	N	0.181	neutral	N	0.459710139	None	None	N
P/V	0.1639	likely_benign	0.1669	benign	-0.22	Destabilizing	0.007	N	0.179	neutral	None	None	None	None	N
P/W	0.6275	likely_pathogenic	0.6358	pathogenic	-0.69	Destabilizing	0.991	D	0.43	neutral	None	None	None	None	N
P/Y	0.4206	ambiguous	0.424	ambiguous	-0.386	Destabilizing	0.965	D	0.489	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.