TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23091	69496;69497;69498	chr2:178577064;178577063;178577062	chr2:179441791;179441790;179441789
N2AB	21450	64573;64574;64575	chr2:178577064;178577063;178577062	chr2:179441791;179441790;179441789
N2A	20523	61792;61793;61794	chr2:178577064;178577063;178577062	chr2:179441791;179441790;179441789
N2B	14026	42301;42302;42303	chr2:178577064;178577063;178577062	chr2:179441791;179441790;179441789
Novex-1	14151	42676;42677;42678	chr2:178577064;178577063;178577062	chr2:179441791;179441790;179441789
Novex-2	14218	42877;42878;42879	chr2:178577064;178577063;178577062	chr2:179441791;179441790;179441789
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Fn3-55
• Domain position: 52
• Structural Position: 69
• Q(SASA): 0.1745
• 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/F	None	None	0.295	N	0.433	0.365	0.539388553722	gnomAD-4.0.0	1.59195E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02572E-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	0.057	likely_benign	0.0554	benign	-0.441	Destabilizing	None	N	0.129	neutral	N	0.431268036	None	None	N
S/C	0.1092	likely_benign	0.1142	benign	-0.377	Destabilizing	0.295	N	0.449	neutral	D	0.523178119	None	None	N
S/D	0.3772	ambiguous	0.3237	benign	-0.005	Destabilizing	0.072	N	0.391	neutral	None	None	None	None	N
S/E	0.4548	ambiguous	0.4097	ambiguous	0.004	Stabilizing	0.072	N	0.361	neutral	None	None	None	None	N
S/F	0.2772	likely_benign	0.2657	benign	-0.607	Destabilizing	0.295	N	0.433	neutral	N	0.481803718	None	None	N
S/G	0.0983	likely_benign	0.0961	benign	-0.697	Destabilizing	0.016	N	0.295	neutral	None	None	None	None	N
S/H	0.3533	ambiguous	0.3366	benign	-1.126	Destabilizing	0.628	D	0.441	neutral	None	None	None	None	N
S/I	0.269	likely_benign	0.249	benign	0.127	Stabilizing	0.016	N	0.379	neutral	None	None	None	None	N
S/K	0.614	likely_pathogenic	0.564	pathogenic	-0.598	Destabilizing	0.072	N	0.364	neutral	None	None	None	None	N
S/L	0.1188	likely_benign	0.1209	benign	0.127	Stabilizing	0.016	N	0.39	neutral	None	None	None	None	N
S/M	0.1758	likely_benign	0.1733	benign	0.118	Stabilizing	0.356	N	0.457	neutral	None	None	None	None	N
S/N	0.1816	likely_benign	0.1707	benign	-0.588	Destabilizing	0.136	N	0.454	neutral	None	None	None	None	N
S/P	0.8924	likely_pathogenic	0.8864	pathogenic	-0.027	Destabilizing	0.055	N	0.424	neutral	N	0.469219645	None	None	N
S/Q	0.4328	ambiguous	0.3944	ambiguous	-0.63	Destabilizing	0.356	N	0.465	neutral	None	None	None	None	N
S/R	0.5884	likely_pathogenic	0.5526	ambiguous	-0.548	Destabilizing	0.072	N	0.407	neutral	None	None	None	None	N
S/T	0.0834	likely_benign	0.0827	benign	-0.551	Destabilizing	0.012	N	0.367	neutral	N	0.458489136	None	None	N
S/V	0.1903	likely_benign	0.1747	benign	-0.027	Destabilizing	None	N	0.296	neutral	None	None	None	None	N
S/W	0.3934	ambiguous	0.4129	ambiguous	-0.68	Destabilizing	0.864	D	0.528	neutral	None	None	None	None	N
S/Y	0.2523	likely_benign	0.2421	benign	-0.369	Destabilizing	0.295	N	0.439	neutral	N	0.475328244	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.