TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23124	69595;69596;69597	chr2:178576965;178576964;178576963	chr2:179441692;179441691;179441690
N2AB	21483	64672;64673;64674	chr2:178576965;178576964;178576963	chr2:179441692;179441691;179441690
N2A	20556	61891;61892;61893	chr2:178576965;178576964;178576963	chr2:179441692;179441691;179441690
N2B	14059	42400;42401;42402	chr2:178576965;178576964;178576963	chr2:179441692;179441691;179441690
Novex-1	14184	42775;42776;42777	chr2:178576965;178576964;178576963	chr2:179441692;179441691;179441690
Novex-2	14251	42976;42977;42978	chr2:178576965;178576964;178576963	chr2:179441692;179441691;179441690
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: Fn3-55
• Domain position: 85
• Structural Position: 119
• Q(SASA): 0.3953
• Predicted PPI site: I

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/Q	None	None	0.904	N	0.623	0.218	0.314716216878	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-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
E/A	0.1877	likely_benign	0.1612	benign	-0.302	Destabilizing	0.822	D	0.612	neutral	N	0.483218842	None	None	I
E/C	0.8483	likely_pathogenic	0.794	pathogenic	-0.173	Destabilizing	0.998	D	0.794	deleterious	None	None	None	None	I
E/D	0.0972	likely_benign	0.0833	benign	-0.361	Destabilizing	0.002	N	0.137	neutral	N	0.47844312	None	None	I
E/F	0.7482	likely_pathogenic	0.6879	pathogenic	-0.116	Destabilizing	0.993	D	0.731	prob.delet.	None	None	None	None	I
E/G	0.2499	likely_benign	0.2263	benign	-0.491	Destabilizing	0.822	D	0.601	neutral	N	0.499499445	None	None	I
E/H	0.5636	ambiguous	0.5207	ambiguous	0.272	Stabilizing	0.993	D	0.563	neutral	None	None	None	None	I
E/I	0.3244	likely_benign	0.254	benign	0.158	Stabilizing	0.978	D	0.711	prob.delet.	None	None	None	None	I
E/K	0.206	likely_benign	0.1868	benign	0.349	Stabilizing	0.822	D	0.607	neutral	N	0.51913495	None	None	I
E/L	0.3768	ambiguous	0.2982	benign	0.158	Stabilizing	0.978	D	0.669	neutral	None	None	None	None	I
E/M	0.4556	ambiguous	0.3762	ambiguous	0.109	Stabilizing	0.998	D	0.71	prob.delet.	None	None	None	None	I
E/N	0.2622	likely_benign	0.2201	benign	-0.056	Destabilizing	0.754	D	0.605	neutral	None	None	None	None	I
E/P	0.3849	ambiguous	0.3449	ambiguous	0.025	Stabilizing	0.978	D	0.636	neutral	None	None	None	None	I
E/Q	0.175	likely_benign	0.1582	benign	-0.014	Destabilizing	0.904	D	0.623	neutral	N	0.467836839	None	None	I
E/R	0.365	ambiguous	0.344	ambiguous	0.623	Stabilizing	0.978	D	0.593	neutral	None	None	None	None	I
E/S	0.235	likely_benign	0.1995	benign	-0.198	Destabilizing	0.86	D	0.57	neutral	None	None	None	None	I
E/T	0.2771	likely_benign	0.2229	benign	-0.036	Destabilizing	0.86	D	0.649	neutral	None	None	None	None	I
E/V	0.2102	likely_benign	0.1655	benign	0.025	Stabilizing	0.97	D	0.6	neutral	N	0.517038794	None	None	I
E/W	0.923	likely_pathogenic	0.9066	pathogenic	0.046	Stabilizing	0.998	D	0.781	deleterious	None	None	None	None	I
E/Y	0.6237	likely_pathogenic	0.5671	pathogenic	0.133	Stabilizing	0.993	D	0.716	prob.delet.	None	None	None	None	I

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.