TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8469	25630;25631;25632	chr2:178717329;178717328;178717327	chr2:179582056;179582055;179582054
N2AB	8152	24679;24680;24681	chr2:178717329;178717328;178717327	chr2:179582056;179582055;179582054
N2A	7225	21898;21899;21900	chr2:178717329;178717328;178717327	chr2:179582056;179582055;179582054
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-70
• Domain position: 14
• Structural Position: 23
• Q(SASA): 0.5832
• 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
L/F	None	None	0.893	N	0.255	0.193	0.227260227426	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
L/A	0.1498	likely_benign	0.1444	benign	-0.8	Destabilizing	0.096	N	0.134	neutral	None	None	None	None	N
L/C	0.6983	likely_pathogenic	0.7093	pathogenic	-0.644	Destabilizing	0.998	D	0.236	neutral	None	None	None	None	N
L/D	0.7418	likely_pathogenic	0.7189	pathogenic	-0.285	Destabilizing	0.983	D	0.347	neutral	None	None	None	None	N
L/E	0.3981	ambiguous	0.3693	ambiguous	-0.36	Destabilizing	0.855	D	0.347	neutral	None	None	None	None	N
L/F	0.1326	likely_benign	0.1492	benign	-0.691	Destabilizing	0.893	D	0.255	neutral	N	0.461794954	None	None	N
L/G	0.4701	ambiguous	0.4622	ambiguous	-1.0	Destabilizing	0.888	D	0.39	neutral	None	None	None	None	N
L/H	0.2932	likely_benign	0.2995	benign	-0.243	Destabilizing	0.018	N	0.408	neutral	N	0.473658238	None	None	N
L/I	0.0746	likely_benign	0.0794	benign	-0.384	Destabilizing	0.001	N	0.261	neutral	N	0.417690158	None	None	N
L/K	0.3714	ambiguous	0.3431	ambiguous	-0.495	Destabilizing	0.322	N	0.344	neutral	None	None	None	None	N
L/M	0.1067	likely_benign	0.107	benign	-0.426	Destabilizing	0.77	D	0.264	neutral	None	None	None	None	N
L/N	0.408	ambiguous	0.3924	ambiguous	-0.263	Destabilizing	0.965	D	0.344	neutral	None	None	None	None	N
L/P	0.203	likely_benign	0.1891	benign	-0.489	Destabilizing	0.977	D	0.357	neutral	N	0.474871592	None	None	N
L/Q	0.1563	likely_benign	0.1547	benign	-0.482	Destabilizing	0.959	D	0.319	neutral	None	None	None	None	N
L/R	0.2745	likely_benign	0.2683	benign	0.077	Stabilizing	0.944	D	0.33	neutral	N	0.462923802	None	None	N
L/S	0.2096	likely_benign	0.2033	benign	-0.746	Destabilizing	0.8	D	0.351	neutral	None	None	None	None	N
L/T	0.1683	likely_benign	0.1682	benign	-0.71	Destabilizing	0.031	N	0.185	neutral	None	None	None	None	N
L/V	0.0751	likely_benign	0.0769	benign	-0.489	Destabilizing	0.003	N	0.121	neutral	N	0.383998872	None	None	N
L/W	0.2972	likely_benign	0.3147	benign	-0.708	Destabilizing	0.999	D	0.359	neutral	None	None	None	None	N
L/Y	0.4225	ambiguous	0.4462	ambiguous	-0.468	Destabilizing	0.566	D	0.279	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.