TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27416	82471;82472;82473	chr2:178563886;178563885;178563884	chr2:179428613;179428612;179428611
N2AB	25775	77548;77549;77550	chr2:178563886;178563885;178563884	chr2:179428613;179428612;179428611
N2A	24848	74767;74768;74769	chr2:178563886;178563885;178563884	chr2:179428613;179428612;179428611
N2B	18351	55276;55277;55278	chr2:178563886;178563885;178563884	chr2:179428613;179428612;179428611
Novex-1	18476	55651;55652;55653	chr2:178563886;178563885;178563884	chr2:179428613;179428612;179428611
Novex-2	18543	55852;55853;55854	chr2:178563886;178563885;178563884	chr2:179428613;179428612;179428611
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: Fn3-87
• Domain position: 48
• Structural Position: 64
• Q(SASA): 0.57
• 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
S/F	None	None	0.994	N	0.608	0.443	0.515092168024	gnomAD-4.0.0	1.36846E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79901E-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
S/A	0.0819	likely_benign	0.0903	benign	-0.558	Destabilizing	0.773	D	0.448	neutral	N	0.476365607	None	None	I
S/C	0.1186	likely_benign	0.1372	benign	-0.443	Destabilizing	0.999	D	0.537	neutral	N	0.486767696	None	None	I
S/D	0.8262	likely_pathogenic	0.873	pathogenic	0.257	Stabilizing	0.957	D	0.403	neutral	None	None	None	None	I
S/E	0.8431	likely_pathogenic	0.8785	pathogenic	0.199	Stabilizing	0.916	D	0.426	neutral	None	None	None	None	I
S/F	0.3649	ambiguous	0.4133	ambiguous	-0.939	Destabilizing	0.994	D	0.608	neutral	N	0.480019746	None	None	I
S/G	0.1618	likely_benign	0.1883	benign	-0.724	Destabilizing	0.916	D	0.419	neutral	None	None	None	None	I
S/H	0.6191	likely_pathogenic	0.6754	pathogenic	-1.057	Destabilizing	0.997	D	0.497	neutral	None	None	None	None	I
S/I	0.2481	likely_benign	0.2557	benign	-0.242	Destabilizing	0.987	D	0.606	neutral	None	None	None	None	I
S/K	0.9357	likely_pathogenic	0.9538	pathogenic	-0.585	Destabilizing	0.845	D	0.427	neutral	None	None	None	None	I
S/L	0.1009	likely_benign	0.1086	benign	-0.242	Destabilizing	0.916	D	0.506	neutral	None	None	None	None	I
S/M	0.2574	likely_benign	0.2662	benign	-0.159	Destabilizing	0.999	D	0.504	neutral	None	None	None	None	I
S/N	0.2792	likely_benign	0.3272	benign	-0.36	Destabilizing	0.916	D	0.42	neutral	None	None	None	None	I
S/P	0.6588	likely_pathogenic	0.704	pathogenic	-0.316	Destabilizing	0.994	D	0.497	neutral	N	0.517558869	None	None	I
S/Q	0.7159	likely_pathogenic	0.7583	pathogenic	-0.539	Destabilizing	0.975	D	0.458	neutral	None	None	None	None	I
S/R	0.8826	likely_pathogenic	0.9134	pathogenic	-0.369	Destabilizing	0.073	N	0.345	neutral	None	None	None	None	I
S/T	0.1202	likely_benign	0.1273	benign	-0.47	Destabilizing	0.892	D	0.436	neutral	N	0.440983597	None	None	I
S/V	0.2176	likely_benign	0.2254	benign	-0.316	Destabilizing	0.987	D	0.597	neutral	None	None	None	None	I
S/W	0.5386	ambiguous	0.5873	pathogenic	-0.921	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	I
S/Y	0.3526	ambiguous	0.4017	ambiguous	-0.662	Destabilizing	0.994	D	0.61	neutral	N	0.486514206	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.