TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27576	82951;82952;82953	chr2:178563406;178563405;178563404	chr2:179428133;179428132;179428131
N2AB	25935	78028;78029;78030	chr2:178563406;178563405;178563404	chr2:179428133;179428132;179428131
N2A	25008	75247;75248;75249	chr2:178563406;178563405;178563404	chr2:179428133;179428132;179428131
N2B	18511	55756;55757;55758	chr2:178563406;178563405;178563404	chr2:179428133;179428132;179428131
Novex-1	18636	56131;56132;56133	chr2:178563406;178563405;178563404	chr2:179428133;179428132;179428131
Novex-2	18703	56332;56333;56334	chr2:178563406;178563405;178563404	chr2:179428133;179428132;179428131
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: Fn3-89
• Domain position: 7
• Structural Position: 7
• Q(SASA): 0.7969
• 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/S	rs773621324	0.444	0.999	D	0.569	0.327	0.273938319068	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	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	0.3439	ambiguous	0.3068	benign	-0.332	Destabilizing	1.0	D	0.645	neutral	None	None	None	None	N
N/C	0.2741	likely_benign	0.2663	benign	0.332	Stabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
N/D	0.4603	ambiguous	0.3821	ambiguous	0.019	Stabilizing	0.999	D	0.597	neutral	N	0.48902826	None	None	N
N/E	0.7688	likely_pathogenic	0.6918	pathogenic	-0.024	Destabilizing	0.999	D	0.662	neutral	None	None	None	None	N
N/F	0.5248	ambiguous	0.5108	ambiguous	-0.741	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
N/G	0.4331	ambiguous	0.4078	ambiguous	-0.493	Destabilizing	0.999	D	0.575	neutral	None	None	None	None	N
N/H	0.141	likely_benign	0.1353	benign	-0.549	Destabilizing	1.0	D	0.587	neutral	N	0.488532577	None	None	N
N/I	0.2701	likely_benign	0.2478	benign	0.001	Stabilizing	1.0	D	0.71	prob.delet.	N	0.508598615	None	None	N
N/K	0.6544	likely_pathogenic	0.5761	pathogenic	0.087	Stabilizing	1.0	D	0.671	neutral	N	0.515734859	None	None	N
N/L	0.2723	likely_benign	0.2493	benign	0.001	Stabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
N/M	0.3824	ambiguous	0.3681	ambiguous	0.373	Stabilizing	1.0	D	0.664	neutral	None	None	None	None	N
N/P	0.824	likely_pathogenic	0.7768	pathogenic	-0.084	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
N/Q	0.5187	ambiguous	0.4731	ambiguous	-0.401	Destabilizing	1.0	D	0.623	neutral	None	None	None	None	N
N/R	0.6343	likely_pathogenic	0.5815	pathogenic	0.153	Stabilizing	1.0	D	0.651	neutral	None	None	None	None	N
N/S	0.1027	likely_benign	0.0942	benign	-0.135	Destabilizing	0.999	D	0.569	neutral	D	0.524797059	None	None	N
N/T	0.2156	likely_benign	0.1934	benign	-0.04	Destabilizing	0.999	D	0.661	neutral	D	0.529280159	None	None	N
N/V	0.2659	likely_benign	0.2491	benign	-0.084	Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	N
N/W	0.8555	likely_pathogenic	0.8314	pathogenic	-0.735	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
N/Y	0.2121	likely_benign	0.1906	benign	-0.466	Destabilizing	1.0	D	0.685	prob.neutral	D	0.532236278	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.