TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27401	82426;82427;82428	chr2:178563931;178563930;178563929	chr2:179428658;179428657;179428656
N2AB	25760	77503;77504;77505	chr2:178563931;178563930;178563929	chr2:179428658;179428657;179428656
N2A	24833	74722;74723;74724	chr2:178563931;178563930;178563929	chr2:179428658;179428657;179428656
N2B	18336	55231;55232;55233	chr2:178563931;178563930;178563929	chr2:179428658;179428657;179428656
Novex-1	18461	55606;55607;55608	chr2:178563931;178563930;178563929	chr2:179428658;179428657;179428656
Novex-2	18528	55807;55808;55809	chr2:178563931;178563930;178563929	chr2:179428658;179428657;179428656
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: Fn3-87
• Domain position: 33
• Structural Position: 34
• Q(SASA): 0.6909
• 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
N/D	rs1365991014	0.394	None	N	0.079	0.112	0.104622674875	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	0	1.65837E-04
N/D	rs1365991014	0.394	None	N	0.079	0.112	0.104622674875	gnomAD-4.0.0	3.18284E-06	None	None	None	None	I	None	0	2.28676E-05	None	0	0	None	0	0	2.85866E-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	0.0788	likely_benign	0.0924	benign	-0.181	Destabilizing	0.007	N	0.448	neutral	None	None	None	None	I
N/C	0.139	likely_benign	0.1652	benign	0.369	Stabilizing	0.676	D	0.503	neutral	None	None	None	None	I
N/D	0.0857	likely_benign	0.0953	benign	0.181	Stabilizing	None	N	0.079	neutral	N	0.416757156	None	None	I
N/E	0.1776	likely_benign	0.1984	benign	0.126	Stabilizing	0.016	N	0.369	neutral	None	None	None	None	I
N/F	0.2974	likely_benign	0.3511	ambiguous	-0.695	Destabilizing	0.356	N	0.533	neutral	None	None	None	None	I
N/G	0.1167	likely_benign	0.1361	benign	-0.307	Destabilizing	0.007	N	0.285	neutral	None	None	None	None	I
N/H	0.0883	likely_benign	0.0994	benign	-0.37	Destabilizing	0.295	N	0.407	neutral	N	0.466359257	None	None	I
N/I	0.1101	likely_benign	0.1237	benign	0.056	Stabilizing	0.171	N	0.521	neutral	N	0.469764922	None	None	I
N/K	0.1451	likely_benign	0.1628	benign	0.205	Stabilizing	0.012	N	0.366	neutral	N	0.372312946	None	None	I
N/L	0.1204	likely_benign	0.131	benign	0.056	Stabilizing	0.072	N	0.561	neutral	None	None	None	None	I
N/M	0.1814	likely_benign	0.2042	benign	0.305	Stabilizing	0.628	D	0.502	neutral	None	None	None	None	I
N/P	0.1461	likely_benign	0.1592	benign	0.002	Stabilizing	0.072	N	0.513	neutral	None	None	None	None	I
N/Q	0.1694	likely_benign	0.1958	benign	-0.164	Destabilizing	0.072	N	0.382	neutral	None	None	None	None	I
N/R	0.1788	likely_benign	0.2122	benign	0.256	Stabilizing	0.072	N	0.383	neutral	None	None	None	None	I
N/S	0.0539	likely_benign	0.0583	benign	0.063	Stabilizing	None	N	0.075	neutral	N	0.428147586	None	None	I
N/T	0.0686	likely_benign	0.0757	benign	0.135	Stabilizing	0.012	N	0.372	neutral	N	0.448253499	None	None	I
N/V	0.0998	likely_benign	0.1104	benign	0.002	Stabilizing	0.072	N	0.533	neutral	None	None	None	None	I
N/W	0.5664	likely_pathogenic	0.6395	pathogenic	-0.76	Destabilizing	0.864	D	0.547	neutral	None	None	None	None	I
N/Y	0.1313	likely_benign	0.1429	benign	-0.455	Destabilizing	0.295	N	0.521	neutral	N	0.507109802	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.