TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7503	22732;22733;22734	chr2:178722280;178722279;178722278	chr2:179587007;179587006;179587005
N2AB	7186	21781;21782;21783	chr2:178722280;178722279;178722278	chr2:179587007;179587006;179587005
N2A	6259	19000;19001;19002	chr2:178722280;178722279;178722278	chr2:179587007;179587006;179587005
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: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-59
• Domain position: 85
• Structural Position: 171
• Q(SASA): 0.2884
• 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
S/R	None	None	0.001	N	0.269	0.185	0.297375071883	gnomAD-4.0.0	3.45723E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.62171E-06	1.21021E-05	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
S/A	0.0902	likely_benign	0.0868	benign	-0.616	Destabilizing	0.002	N	0.318	neutral	None	None	None	None	N
S/C	0.2202	likely_benign	0.1605	benign	-0.335	Destabilizing	0.835	D	0.546	neutral	D	0.52522311	None	None	N
S/D	0.4566	ambiguous	0.4315	ambiguous	-0.119	Destabilizing	0.049	N	0.379	neutral	None	None	None	None	N
S/E	0.5251	ambiguous	0.502	ambiguous	-0.21	Destabilizing	0.005	N	0.215	neutral	None	None	None	None	N
S/F	0.1532	likely_benign	0.1482	benign	-1.259	Destabilizing	0.869	D	0.607	neutral	None	None	None	None	N
S/G	0.1226	likely_benign	0.1191	benign	-0.718	Destabilizing	0.126	N	0.375	neutral	N	0.50832017	None	None	N
S/H	0.2908	likely_benign	0.2802	benign	-1.324	Destabilizing	0.869	D	0.564	neutral	None	None	None	None	N
S/I	0.1463	likely_benign	0.1402	benign	-0.468	Destabilizing	0.553	D	0.634	neutral	N	0.521500127	None	None	N
S/K	0.5269	ambiguous	0.5299	ambiguous	-0.455	Destabilizing	0.012	N	0.203	neutral	None	None	None	None	N
S/L	0.1062	likely_benign	0.1023	benign	-0.468	Destabilizing	0.318	N	0.546	neutral	None	None	None	None	N
S/M	0.1864	likely_benign	0.1635	benign	0.015	Stabilizing	0.869	D	0.562	neutral	None	None	None	None	N
S/N	0.1358	likely_benign	0.1223	benign	-0.203	Destabilizing	None	N	0.234	neutral	N	0.496292301	None	None	N
S/P	0.5886	likely_pathogenic	0.551	ambiguous	-0.491	Destabilizing	0.336	N	0.564	neutral	None	None	None	None	N
S/Q	0.4244	ambiguous	0.4141	ambiguous	-0.558	Destabilizing	0.483	N	0.43	neutral	None	None	None	None	N
S/R	0.4124	ambiguous	0.4276	ambiguous	-0.233	Destabilizing	0.001	N	0.269	neutral	N	0.519687602	None	None	N
S/T	0.0674	likely_benign	0.0606	benign	-0.327	Destabilizing	None	N	0.205	neutral	N	0.497906821	None	None	N
S/V	0.1545	likely_benign	0.1468	benign	-0.491	Destabilizing	0.149	N	0.567	neutral	None	None	None	None	N
S/W	0.3392	likely_benign	0.3329	benign	-1.195	Destabilizing	0.987	D	0.652	neutral	None	None	None	None	N
S/Y	0.1828	likely_benign	0.1659	benign	-0.929	Destabilizing	0.869	D	0.61	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.