TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25355	76288;76289;76290	chr2:178570069;178570068;178570067	chr2:179434796;179434795;179434794
N2AB	23714	71365;71366;71367	chr2:178570069;178570068;178570067	chr2:179434796;179434795;179434794
N2A	22787	68584;68585;68586	chr2:178570069;178570068;178570067	chr2:179434796;179434795;179434794
N2B	16290	49093;49094;49095	chr2:178570069;178570068;178570067	chr2:179434796;179434795;179434794
Novex-1	16415	49468;49469;49470	chr2:178570069;178570068;178570067	chr2:179434796;179434795;179434794
Novex-2	16482	49669;49670;49671	chr2:178570069;178570068;178570067	chr2:179434796;179434795;179434794
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Fn3-72
• Domain position: 52
• Structural Position: 69
• Q(SASA): 0.1911
• 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
H/R	rs1399292028	-1.533	0.285	N	0.317	0.154	0.191931220699	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	1.65782E-04
H/R	rs1399292028	-1.533	0.285	N	0.317	0.154	0.191931220699	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
H/R	rs1399292028	-1.533	0.285	N	0.317	0.154	0.191931220699	gnomAD-4.0.0	3.84518E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.18243E-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
H/A	0.3189	likely_benign	0.2707	benign	0.209	Stabilizing	0.103	N	0.334	neutral	None	None	None	None	N
H/C	0.1755	likely_benign	0.1623	benign	0.691	Stabilizing	0.991	D	0.45	neutral	None	None	None	None	N
H/D	0.4138	ambiguous	0.307	benign	-0.219	Destabilizing	0.166	N	0.353	neutral	N	0.432553328	None	None	N
H/E	0.6006	likely_pathogenic	0.4664	ambiguous	-0.155	Destabilizing	0.345	N	0.304	neutral	None	None	None	None	N
H/F	0.4131	ambiguous	0.3741	ambiguous	1.209	Stabilizing	0.965	D	0.442	neutral	None	None	None	None	N
H/G	0.2599	likely_benign	0.2265	benign	-0.12	Destabilizing	0.103	N	0.313	neutral	None	None	None	None	N
H/I	0.3764	ambiguous	0.3427	ambiguous	1.078	Stabilizing	0.722	D	0.451	neutral	None	None	None	None	N
H/K	0.5422	ambiguous	0.4494	ambiguous	0.261	Stabilizing	0.345	N	0.368	neutral	None	None	None	None	N
H/L	0.1652	likely_benign	0.1503	benign	1.078	Stabilizing	0.447	N	0.397	neutral	N	0.427590226	None	None	N
H/M	0.4689	ambiguous	0.4605	ambiguous	0.699	Stabilizing	0.965	D	0.425	neutral	None	None	None	None	N
H/N	0.0475	likely_benign	0.0479	benign	0.108	Stabilizing	None	N	0.092	neutral	N	0.303413008	None	None	N
H/P	0.3966	ambiguous	0.3471	ambiguous	0.813	Stabilizing	0.662	D	0.418	neutral	N	0.459451928	None	None	N
H/Q	0.243	likely_benign	0.1855	benign	0.285	Stabilizing	0.491	N	0.326	neutral	N	0.452485883	None	None	N
H/R	0.338	likely_benign	0.2464	benign	-0.46	Destabilizing	0.285	N	0.317	neutral	N	0.445309195	None	None	N
H/S	0.1208	likely_benign	0.1112	benign	0.251	Stabilizing	0.021	N	0.207	neutral	None	None	None	None	N
H/T	0.1697	likely_benign	0.1601	benign	0.427	Stabilizing	0.209	N	0.365	neutral	None	None	None	None	N
H/V	0.3031	likely_benign	0.2706	benign	0.813	Stabilizing	0.722	D	0.426	neutral	None	None	None	None	N
H/W	0.6451	likely_pathogenic	0.5772	pathogenic	1.3	Stabilizing	0.991	D	0.425	neutral	None	None	None	None	N
H/Y	0.1614	likely_benign	0.1322	benign	1.465	Stabilizing	0.856	D	0.357	neutral	N	0.408351104	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.