TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23071	69436;69437;69438	chr2:178577124;178577123;178577122	chr2:179441851;179441850;179441849
N2AB	21430	64513;64514;64515	chr2:178577124;178577123;178577122	chr2:179441851;179441850;179441849
N2A	20503	61732;61733;61734	chr2:178577124;178577123;178577122	chr2:179441851;179441850;179441849
N2B	14006	42241;42242;42243	chr2:178577124;178577123;178577122	chr2:179441851;179441850;179441849
Novex-1	14131	42616;42617;42618	chr2:178577124;178577123;178577122	chr2:179441851;179441850;179441849
Novex-2	14198	42817;42818;42819	chr2:178577124;178577123;178577122	chr2:179441851;179441850;179441849
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-55
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.6792
• 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
P/L	rs367664195	-0.138	0.822	N	0.531	0.331	None	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
P/S	None	None	0.07	N	0.167	0.138	0.168933306366	gnomAD-4.0.0	1.36879E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79929E-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
P/A	0.0697	likely_benign	0.0715	benign	-0.46	Destabilizing	0.489	N	0.463	neutral	N	0.519791098	None	None	I
P/C	0.4386	ambiguous	0.4254	ambiguous	-0.56	Destabilizing	0.998	D	0.623	neutral	None	None	None	None	I
P/D	0.3229	likely_benign	0.3429	ambiguous	-0.214	Destabilizing	0.754	D	0.467	neutral	None	None	None	None	I
P/E	0.2076	likely_benign	0.2133	benign	-0.339	Destabilizing	0.019	N	0.279	neutral	None	None	None	None	I
P/F	0.4598	ambiguous	0.4648	ambiguous	-0.773	Destabilizing	0.993	D	0.599	neutral	None	None	None	None	I
P/G	0.2923	likely_benign	0.3178	benign	-0.582	Destabilizing	0.86	D	0.511	neutral	None	None	None	None	I
P/H	0.1882	likely_benign	0.1895	benign	-0.2	Destabilizing	0.994	D	0.571	neutral	None	None	None	None	I
P/I	0.231	likely_benign	0.2347	benign	-0.296	Destabilizing	0.978	D	0.609	neutral	None	None	None	None	I
P/K	0.2404	likely_benign	0.2217	benign	-0.303	Destabilizing	0.754	D	0.461	neutral	None	None	None	None	I
P/L	0.1177	likely_benign	0.1142	benign	-0.296	Destabilizing	0.822	D	0.531	neutral	N	0.490833074	None	None	I
P/M	0.2338	likely_benign	0.2332	benign	-0.227	Destabilizing	0.998	D	0.57	neutral	None	None	None	None	I
P/N	0.2427	likely_benign	0.2508	benign	-0.041	Destabilizing	0.86	D	0.495	neutral	None	None	None	None	I
P/Q	0.139	likely_benign	0.1395	benign	-0.315	Destabilizing	0.89	D	0.459	neutral	N	0.496060086	None	None	I
P/R	0.1925	likely_benign	0.1915	benign	0.211	Stabilizing	0.942	D	0.552	neutral	N	0.486780922	None	None	I
P/S	0.1149	likely_benign	0.1171	benign	-0.415	Destabilizing	0.07	N	0.167	neutral	N	0.516558791	None	None	I
P/T	0.0939	likely_benign	0.0941	benign	-0.438	Destabilizing	0.698	D	0.463	neutral	N	0.471612729	None	None	I
P/V	0.1477	likely_benign	0.1539	benign	-0.316	Destabilizing	0.926	D	0.495	neutral	None	None	None	None	I
P/W	0.6699	likely_pathogenic	0.6916	pathogenic	-0.839	Destabilizing	0.998	D	0.703	prob.neutral	None	None	None	None	I
P/Y	0.4279	ambiguous	0.4393	ambiguous	-0.519	Destabilizing	0.993	D	0.6	neutral	None	None	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.