TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21128	63607;63608;63609	chr2:178588025;178588024;178588023	chr2:179452752;179452751;179452750
N2AB	19487	58684;58685;58686	chr2:178588025;178588024;178588023	chr2:179452752;179452751;179452750
N2A	18560	55903;55904;55905	chr2:178588025;178588024;178588023	chr2:179452752;179452751;179452750
N2B	12063	36412;36413;36414	chr2:178588025;178588024;178588023	chr2:179452752;179452751;179452750
Novex-1	12188	36787;36788;36789	chr2:178588025;178588024;178588023	chr2:179452752;179452751;179452750
Novex-2	12255	36988;36989;36990	chr2:178588025;178588024;178588023	chr2:179452752;179452751;179452750
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: Fn3-41
• Domain position: 65
• Structural Position: 89
• Q(SASA): 0.2613
• 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	rs2049409571	None	0.014	N	0.329	0.06	0.163833314356	gnomAD-4.0.0	2.05362E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69926E-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
K/A	0.1909	likely_benign	0.2543	benign	-0.955	Destabilizing	0.002	N	0.335	neutral	None	None	None	None	N
K/C	0.3702	ambiguous	0.4484	ambiguous	-1.027	Destabilizing	0.497	N	0.558	neutral	None	None	None	None	N
K/D	0.4152	ambiguous	0.4606	ambiguous	-0.679	Destabilizing	0.018	N	0.413	neutral	None	None	None	None	N
K/E	0.1688	likely_benign	0.1917	benign	-0.482	Destabilizing	0.014	N	0.329	neutral	N	0.426826929	None	None	N
K/F	0.697	likely_pathogenic	0.7856	pathogenic	-0.554	Destabilizing	0.044	N	0.567	neutral	None	None	None	None	N
K/G	0.238	likely_benign	0.2863	benign	-1.329	Destabilizing	0.018	N	0.4	neutral	None	None	None	None	N
K/H	0.2547	likely_benign	0.2679	benign	-1.081	Destabilizing	0.245	N	0.487	neutral	None	None	None	None	N
K/I	0.3588	ambiguous	0.4724	ambiguous	0.053	Stabilizing	0.009	N	0.456	neutral	None	None	None	None	N
K/L	0.2006	likely_benign	0.2768	benign	0.053	Stabilizing	0.001	N	0.401	neutral	None	None	None	None	N
K/M	0.0948	likely_benign	0.1565	benign	-0.369	Destabilizing	None	N	0.27	neutral	N	0.451511943	None	None	N
K/N	0.2099	likely_benign	0.2598	benign	-1.03	Destabilizing	0.014	N	0.326	neutral	N	0.439697439	None	None	N
K/P	0.3272	likely_benign	0.3381	benign	-0.259	Destabilizing	None	N	0.272	neutral	None	None	None	None	N
K/Q	0.1096	likely_benign	0.1148	benign	-0.893	Destabilizing	0.014	N	0.359	neutral	N	0.451338585	None	None	N
K/R	0.0812	likely_benign	0.0788	benign	-0.33	Destabilizing	None	N	0.197	neutral	N	0.420130244	None	None	N
K/S	0.2235	likely_benign	0.3004	benign	-1.628	Destabilizing	0.004	N	0.295	neutral	None	None	None	None	N
K/T	0.0601	likely_benign	0.0925	benign	-1.207	Destabilizing	None	N	0.26	neutral	N	0.314728001	None	None	N
K/V	0.2314	likely_benign	0.3334	benign	-0.259	Destabilizing	0.004	N	0.398	neutral	None	None	None	None	N
K/W	0.6905	likely_pathogenic	0.7124	pathogenic	-0.509	Destabilizing	0.788	D	0.567	neutral	None	None	None	None	N
K/Y	0.5211	ambiguous	0.5749	pathogenic	-0.213	Destabilizing	0.085	N	0.604	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.