TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26677	80254;80255;80256	chr2:178566103;178566102;178566101	chr2:179430830;179430829;179430828
N2AB	25036	75331;75332;75333	chr2:178566103;178566102;178566101	chr2:179430830;179430829;179430828
N2A	24109	72550;72551;72552	chr2:178566103;178566102;178566101	chr2:179430830;179430829;179430828
N2B	17612	53059;53060;53061	chr2:178566103;178566102;178566101	chr2:179430830;179430829;179430828
Novex-1	17737	53434;53435;53436	chr2:178566103;178566102;178566101	chr2:179430830;179430829;179430828
Novex-2	17804	53635;53636;53637	chr2:178566103;178566102;178566101	chr2:179430830;179430829;179430828
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-138
• Domain position: 84
• Structural Position: 173
• Q(SASA): 0.3849
• 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
T/S	rs2154165331	None	0.034	N	0.159	0.118	0.233785782151	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
T/A	0.0979	likely_benign	0.0884	benign	-1.107	Destabilizing	0.309	N	0.388	neutral	N	0.494544328	None	None	N
T/C	0.4367	ambiguous	0.4269	ambiguous	-0.668	Destabilizing	0.996	D	0.52	neutral	None	None	None	None	N
T/D	0.6499	likely_pathogenic	0.6012	pathogenic	0.251	Stabilizing	0.742	D	0.495	neutral	None	None	None	None	N
T/E	0.6394	likely_pathogenic	0.5834	pathogenic	0.311	Stabilizing	0.59	D	0.505	neutral	None	None	None	None	N
T/F	0.2918	likely_benign	0.2627	benign	-1.073	Destabilizing	0.984	D	0.601	neutral	None	None	None	None	N
T/G	0.3337	likely_benign	0.3162	benign	-1.402	Destabilizing	0.742	D	0.539	neutral	None	None	None	None	N
T/H	0.3495	ambiguous	0.3285	benign	-1.537	Destabilizing	0.987	D	0.575	neutral	None	None	None	None	N
T/I	0.1659	likely_benign	0.1608	benign	-0.39	Destabilizing	0.939	D	0.562	neutral	N	0.495426663	None	None	N
T/K	0.5264	ambiguous	0.4817	ambiguous	-0.403	Destabilizing	0.009	N	0.262	neutral	None	None	None	None	N
T/L	0.1058	likely_benign	0.097	benign	-0.39	Destabilizing	0.742	D	0.505	neutral	None	None	None	None	N
T/M	0.0793	likely_benign	0.0822	benign	-0.234	Destabilizing	0.984	D	0.539	neutral	None	None	None	None	N
T/N	0.1289	likely_benign	0.1213	benign	-0.46	Destabilizing	0.684	D	0.431	neutral	N	0.433242053	None	None	N
T/P	0.2342	likely_benign	0.2174	benign	-0.598	Destabilizing	0.939	D	0.555	neutral	D	0.523613342	None	None	N
T/Q	0.3786	ambiguous	0.359	ambiguous	-0.525	Destabilizing	0.91	D	0.56	neutral	None	None	None	None	N
T/R	0.4552	ambiguous	0.4044	ambiguous	-0.367	Destabilizing	0.59	D	0.543	neutral	None	None	None	None	N
T/S	0.1193	likely_benign	0.1104	benign	-0.92	Destabilizing	0.034	N	0.159	neutral	N	0.445149771	None	None	N
T/V	0.1342	likely_benign	0.1277	benign	-0.598	Destabilizing	0.742	D	0.439	neutral	None	None	None	None	N
T/W	0.6547	likely_pathogenic	0.6557	pathogenic	-0.927	Destabilizing	0.996	D	0.604	neutral	None	None	None	None	N
T/Y	0.3272	likely_benign	0.3104	benign	-0.683	Destabilizing	0.984	D	0.595	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.