TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26397	79414;79415;79416	chr2:178566943;178566942;178566941	chr2:179431670;179431669;179431668
N2AB	24756	74491;74492;74493	chr2:178566943;178566942;178566941	chr2:179431670;179431669;179431668
N2A	23829	71710;71711;71712	chr2:178566943;178566942;178566941	chr2:179431670;179431669;179431668
N2B	17332	52219;52220;52221	chr2:178566943;178566942;178566941	chr2:179431670;179431669;179431668
Novex-1	17457	52594;52595;52596	chr2:178566943;178566942;178566941	chr2:179431670;179431669;179431668
Novex-2	17524	52795;52796;52797	chr2:178566943;178566942;178566941	chr2:179431670;179431669;179431668
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-80
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.3485
• 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
N/D	rs1349397397	None	0.958	N	0.434	0.399	0.256283259241	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
N/A	0.2671	likely_benign	0.2718	benign	-0.354	Destabilizing	0.938	D	0.503	neutral	None	None	None	None	N
N/C	0.3515	ambiguous	0.325	benign	0.357	Stabilizing	1.0	D	0.659	neutral	None	None	None	None	N
N/D	0.4383	ambiguous	0.3889	ambiguous	0.127	Stabilizing	0.958	D	0.434	neutral	N	0.428032943	None	None	N
N/E	0.8017	likely_pathogenic	0.7685	pathogenic	0.09	Stabilizing	0.938	D	0.445	neutral	None	None	None	None	N
N/F	0.7818	likely_pathogenic	0.7635	pathogenic	-0.724	Destabilizing	1.0	D	0.674	neutral	None	None	None	None	N
N/G	0.32	likely_benign	0.3146	benign	-0.524	Destabilizing	0.968	D	0.407	neutral	None	None	None	None	N
N/H	0.1878	likely_benign	0.1897	benign	-0.556	Destabilizing	0.994	D	0.613	neutral	N	0.480157877	None	None	N
N/I	0.6213	likely_pathogenic	0.5972	pathogenic	0.006	Stabilizing	0.994	D	0.707	prob.neutral	N	0.486260717	None	None	N
N/K	0.7949	likely_pathogenic	0.7751	pathogenic	0.146	Stabilizing	0.067	N	0.288	neutral	N	0.473133301	None	None	N
N/L	0.446	ambiguous	0.447	ambiguous	0.006	Stabilizing	0.991	D	0.643	neutral	None	None	None	None	N
N/M	0.5278	ambiguous	0.5209	ambiguous	0.393	Stabilizing	1.0	D	0.609	neutral	None	None	None	None	N
N/P	0.9522	likely_pathogenic	0.9459	pathogenic	-0.088	Destabilizing	0.995	D	0.649	neutral	None	None	None	None	N
N/Q	0.605	likely_pathogenic	0.6071	pathogenic	-0.337	Destabilizing	0.991	D	0.631	neutral	None	None	None	None	N
N/R	0.7639	likely_pathogenic	0.7456	pathogenic	0.204	Stabilizing	0.982	D	0.539	neutral	None	None	None	None	N
N/S	0.0893	likely_benign	0.0878	benign	-0.102	Destabilizing	0.958	D	0.389	neutral	N	0.445349267	None	None	N
N/T	0.24	likely_benign	0.2325	benign	0.005	Stabilizing	0.958	D	0.482	neutral	N	0.495047369	None	None	N
N/V	0.4425	ambiguous	0.4195	ambiguous	-0.088	Destabilizing	0.991	D	0.7	prob.neutral	None	None	None	None	N
N/W	0.9301	likely_pathogenic	0.9184	pathogenic	-0.689	Destabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	N
N/Y	0.39	ambiguous	0.367	ambiguous	-0.424	Destabilizing	0.998	D	0.649	neutral	N	0.494147529	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.