TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20116	60571;60572;60573	chr2:178591379;178591378;178591377	chr2:179456106;179456105;179456104
N2AB	18475	55648;55649;55650	chr2:178591379;178591378;178591377	chr2:179456106;179456105;179456104
N2A	17548	52867;52868;52869	chr2:178591379;178591378;178591377	chr2:179456106;179456105;179456104
N2B	11051	33376;33377;33378	chr2:178591379;178591378;178591377	chr2:179456106;179456105;179456104
Novex-1	11176	33751;33752;33753	chr2:178591379;178591378;178591377	chr2:179456106;179456105;179456104
Novex-2	11243	33952;33953;33954	chr2:178591379;178591378;178591377	chr2:179456106;179456105;179456104
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGG
• RefSeq wild type template codon: CCC
• Domain: Ig-120
• Domain position: 37
• Structural Position: 52
• Q(SASA): 0.4627
• 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
G/E	None	None	0.338	N	0.464	0.317	0.379881503574	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	2.75482E-04	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
G/A	0.1614	likely_benign	0.1742	benign	-0.194	Destabilizing	0.174	N	0.429	neutral	N	0.493939583	None	None	N
G/C	0.2086	likely_benign	0.2471	benign	-0.85	Destabilizing	0.991	D	0.611	neutral	None	None	None	None	N
G/D	0.1433	likely_benign	0.1495	benign	-0.481	Destabilizing	0.004	N	0.287	neutral	None	None	None	None	N
G/E	0.1841	likely_benign	0.1953	benign	-0.637	Destabilizing	0.338	N	0.464	neutral	N	0.485328302	None	None	N
G/F	0.5365	ambiguous	0.5666	pathogenic	-1.001	Destabilizing	0.906	D	0.593	neutral	None	None	None	None	N
G/H	0.2458	likely_benign	0.2837	benign	-0.333	Destabilizing	0.973	D	0.509	neutral	None	None	None	None	N
G/I	0.3023	likely_benign	0.3244	benign	-0.474	Destabilizing	0.906	D	0.589	neutral	None	None	None	None	N
G/K	0.2607	likely_benign	0.2843	benign	-0.455	Destabilizing	0.404	N	0.469	neutral	None	None	None	None	N
G/L	0.4519	ambiguous	0.4763	ambiguous	-0.474	Destabilizing	0.826	D	0.567	neutral	None	None	None	None	N
G/M	0.4326	ambiguous	0.4553	ambiguous	-0.517	Destabilizing	0.991	D	0.591	neutral	None	None	None	None	N
G/N	0.1543	likely_benign	0.166	benign	-0.207	Destabilizing	0.404	N	0.395	neutral	None	None	None	None	N
G/P	0.8942	likely_pathogenic	0.9091	pathogenic	-0.358	Destabilizing	0.906	D	0.503	neutral	None	None	None	None	N
G/Q	0.2182	likely_benign	0.2408	benign	-0.466	Destabilizing	0.826	D	0.501	neutral	None	None	None	None	N
G/R	0.204	likely_benign	0.229	benign	-0.1	Destabilizing	0.007	N	0.343	neutral	N	0.491217332	None	None	N
G/S	0.0952	likely_benign	0.1007	benign	-0.336	Destabilizing	0.018	N	0.222	neutral	None	None	None	None	N
G/T	0.1558	likely_benign	0.1659	benign	-0.429	Destabilizing	0.404	N	0.467	neutral	None	None	None	None	N
G/V	0.2528	likely_benign	0.2756	benign	-0.358	Destabilizing	0.782	D	0.596	neutral	D	0.524414102	None	None	N
G/W	0.4101	ambiguous	0.4395	ambiguous	-1.099	Destabilizing	0.988	D	0.595	neutral	D	0.535934991	None	None	N
G/Y	0.3642	ambiguous	0.397	ambiguous	-0.78	Destabilizing	0.906	D	0.593	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.