TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31947	96064;96065;96066	chr2:178544390;178544389;178544388	chr2:179409117;179409116;179409115
N2AB	30306	91141;91142;91143	chr2:178544390;178544389;178544388	chr2:179409117;179409116;179409115
N2A	29379	88360;88361;88362	chr2:178544390;178544389;178544388	chr2:179409117;179409116;179409115
N2B	22882	68869;68870;68871	chr2:178544390;178544389;178544388	chr2:179409117;179409116;179409115
Novex-1	23007	69244;69245;69246	chr2:178544390;178544389;178544388	chr2:179409117;179409116;179409115
Novex-2	23074	69445;69446;69447	chr2:178544390;178544389;178544388	chr2:179409117;179409116;179409115
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-121
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.0774
• 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
E/G	None	None	1.0	D	0.763	0.525	0.522290170867	gnomAD-4.0.0	1.59136E-06	None	None	None	None	N	None	0	0	None	0	2.77346E-05	None	0	0	0	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
E/A	0.7511	likely_pathogenic	0.7533	pathogenic	-0.826	Destabilizing	0.999	D	0.703	prob.neutral	N	0.51725176	None	None	N
E/C	0.9735	likely_pathogenic	0.9713	pathogenic	-0.31	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
E/D	0.7238	likely_pathogenic	0.8044	pathogenic	-1.965	Destabilizing	0.999	D	0.668	neutral	N	0.482284244	None	None	N
E/F	0.9836	likely_pathogenic	0.9836	pathogenic	-0.582	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
E/G	0.8668	likely_pathogenic	0.8683	pathogenic	-1.198	Destabilizing	1.0	D	0.763	deleterious	D	0.530382492	None	None	N
E/H	0.9341	likely_pathogenic	0.9422	pathogenic	-0.521	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
E/I	0.9539	likely_pathogenic	0.9489	pathogenic	0.234	Stabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
E/K	0.8897	likely_pathogenic	0.8938	pathogenic	-1.052	Destabilizing	0.999	D	0.685	prob.neutral	N	0.497880057	None	None	N
E/L	0.9326	likely_pathogenic	0.9299	pathogenic	0.234	Stabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
E/M	0.9246	likely_pathogenic	0.9223	pathogenic	0.764	Stabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
E/N	0.9472	likely_pathogenic	0.9623	pathogenic	-1.42	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
E/P	0.9992	likely_pathogenic	0.999	pathogenic	-0.105	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
E/Q	0.4769	ambiguous	0.49	ambiguous	-1.088	Destabilizing	1.0	D	0.755	deleterious	N	0.518961591	None	None	N
E/R	0.9238	likely_pathogenic	0.926	pathogenic	-1.032	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/S	0.8524	likely_pathogenic	0.8692	pathogenic	-1.864	Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	N
E/T	0.9214	likely_pathogenic	0.9243	pathogenic	-1.504	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/V	0.8638	likely_pathogenic	0.859	pathogenic	-0.105	Destabilizing	1.0	D	0.767	deleterious	N	0.506491339	None	None	N
E/W	0.9935	likely_pathogenic	0.9935	pathogenic	-0.845	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
E/Y	0.9723	likely_pathogenic	0.9735	pathogenic	-0.446	Destabilizing	1.0	D	0.798	deleterious	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.