TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17411	52456;52457;52458	chr2:178608780;178608779;178608778	chr2:179473507;179473506;179473505
N2AB	15770	47533;47534;47535	chr2:178608780;178608779;178608778	chr2:179473507;179473506;179473505
N2A	14843	44752;44753;44754	chr2:178608780;178608779;178608778	chr2:179473507;179473506;179473505
N2B	8346	25261;25262;25263	chr2:178608780;178608779;178608778	chr2:179473507;179473506;179473505
Novex-1	8471	25636;25637;25638	chr2:178608780;178608779;178608778	chr2:179473507;179473506;179473505
Novex-2	8538	25837;25838;25839	chr2:178608780;178608779;178608778	chr2:179473507;179473506;179473505
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-14
• Domain position: 43
• Structural Position: 50
• Q(SASA): 0.3287
• 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
K/E	rs1243357204	-0.053	0.425	N	0.326	0.251	0.326345978581	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.63E-05	None	0	None	0	0	0
K/E	rs1243357204	-0.053	0.425	N	0.326	0.251	0.326345978581	gnomAD-4.0.0	1.59381E-06	None	None	None	None	N	None	0	0	None	0	2.78847E-05	None	0	0	0	0	0
K/M	rs1381230857	0.302	0.975	N	0.453	0.425	0.486636631601	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
K/M	rs1381230857	0.302	0.975	N	0.453	0.425	0.486636631601	gnomAD-4.0.0	1.36935E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	3.47222E-04	0	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
K/A	0.2042	likely_benign	0.221	benign	-0.557	Destabilizing	0.329	N	0.397	neutral	None	None	None	None	N
K/C	0.4465	ambiguous	0.4736	ambiguous	-0.543	Destabilizing	0.995	D	0.519	neutral	None	None	None	None	N
K/D	0.5103	ambiguous	0.5229	ambiguous	-0.426	Destabilizing	0.329	N	0.405	neutral	None	None	None	None	N
K/E	0.1735	likely_benign	0.1814	benign	-0.311	Destabilizing	0.425	N	0.326	neutral	N	0.422723124	None	None	N
K/F	0.6963	likely_pathogenic	0.6959	pathogenic	-0.192	Destabilizing	0.981	D	0.538	neutral	None	None	None	None	N
K/G	0.3594	ambiguous	0.3625	ambiguous	-0.943	Destabilizing	0.329	N	0.484	neutral	None	None	None	None	N
K/H	0.2729	likely_benign	0.2865	benign	-1.359	Destabilizing	0.944	D	0.461	neutral	None	None	None	None	N
K/I	0.1676	likely_benign	0.1754	benign	0.451	Stabilizing	0.944	D	0.543	neutral	None	None	None	None	N
K/L	0.2175	likely_benign	0.2421	benign	0.451	Stabilizing	0.704	D	0.508	neutral	None	None	None	None	N
K/M	0.1496	likely_benign	0.153	benign	0.379	Stabilizing	0.975	D	0.453	neutral	N	0.506341798	None	None	N
K/N	0.2552	likely_benign	0.2654	benign	-0.635	Destabilizing	0.001	N	0.134	neutral	N	0.442946467	None	None	N
K/P	0.7233	likely_pathogenic	0.7633	pathogenic	0.146	Stabilizing	0.828	D	0.455	neutral	None	None	None	None	N
K/Q	0.125	likely_benign	0.1297	benign	-0.682	Destabilizing	0.784	D	0.303	neutral	N	0.473690662	None	None	N
K/R	0.0814	likely_benign	0.0818	benign	-0.803	Destabilizing	0.642	D	0.283	neutral	N	0.478963195	None	None	N
K/S	0.2698	likely_benign	0.2863	benign	-1.214	Destabilizing	0.013	N	0.113	neutral	None	None	None	None	N
K/T	0.1092	likely_benign	0.1142	benign	-0.892	Destabilizing	0.27	N	0.401	neutral	N	0.405926874	None	None	N
K/V	0.1472	likely_benign	0.1602	benign	0.146	Stabilizing	0.704	D	0.535	neutral	None	None	None	None	N
K/W	0.7517	likely_pathogenic	0.7495	pathogenic	-0.11	Destabilizing	0.995	D	0.559	neutral	None	None	None	None	N
K/Y	0.5131	ambiguous	0.5132	ambiguous	0.177	Stabilizing	0.981	D	0.537	neutral	None	None	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.