TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3249	9970;9971;9972	chr2:178764770;178764769;178764768	chr2:179629497;179629496;179629495
N2AB	3249	9970;9971;9972	chr2:178764770;178764769;178764768	chr2:179629497;179629496;179629495
N2A	3249	9970;9971;9972	chr2:178764770;178764769;178764768	chr2:179629497;179629496;179629495
N2B	3203	9832;9833;9834	chr2:178764770;178764769;178764768	chr2:179629497;179629496;179629495
Novex-1	3203	9832;9833;9834	chr2:178764770;178764769;178764768	chr2:179629497;179629496;179629495
Novex-2	3203	9832;9833;9834	chr2:178764770;178764769;178764768	chr2:179629497;179629496;179629495
Novex-3	3249	9970;9971;9972	chr2:178764770;178764769;178764768	chr2:179629497;179629496;179629495

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-23
• Domain position: 11
• Structural Position: 14
• Q(SASA): 0.5709
• 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
T/A	rs2090055572	None	0.122	N	0.119	0.18	0.223146558224	gnomAD-4.0.0	2.73689E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59744E-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
T/A	0.0889	likely_benign	0.1256	benign	-0.408	Destabilizing	0.122	N	0.119	neutral	N	0.51014397	None	None	N
T/C	0.5247	ambiguous	0.682	pathogenic	-0.427	Destabilizing	1.0	D	0.472	neutral	None	None	None	None	N
T/D	0.441	ambiguous	0.6435	pathogenic	0.244	Stabilizing	0.97	D	0.43	neutral	None	None	None	None	N
T/E	0.3002	likely_benign	0.4456	ambiguous	0.192	Stabilizing	0.97	D	0.415	neutral	None	None	None	None	N
T/F	0.2623	likely_benign	0.4304	ambiguous	-0.792	Destabilizing	0.999	D	0.516	neutral	None	None	None	None	N
T/G	0.3684	ambiguous	0.551	ambiguous	-0.571	Destabilizing	0.931	D	0.44	neutral	None	None	None	None	N
T/H	0.2542	likely_benign	0.3733	ambiguous	-0.816	Destabilizing	1.0	D	0.515	neutral	None	None	None	None	N
T/I	0.1568	likely_benign	0.2448	benign	-0.093	Destabilizing	0.994	D	0.418	neutral	N	0.512655345	None	None	N
T/K	0.2039	likely_benign	0.2995	benign	-0.42	Destabilizing	0.97	D	0.428	neutral	None	None	None	None	N
T/L	0.1157	likely_benign	0.1768	benign	-0.093	Destabilizing	0.97	D	0.418	neutral	None	None	None	None	N
T/M	0.0859	likely_benign	0.1065	benign	-0.066	Destabilizing	1.0	D	0.467	neutral	None	None	None	None	N
T/N	0.1525	likely_benign	0.2261	benign	-0.316	Destabilizing	0.961	D	0.413	neutral	D	0.559350148	None	None	N
T/P	0.2167	likely_benign	0.4262	ambiguous	-0.168	Destabilizing	0.994	D	0.422	neutral	D	0.618652304	None	None	N
T/Q	0.2309	likely_benign	0.3173	benign	-0.485	Destabilizing	0.996	D	0.453	neutral	None	None	None	None	N
T/R	0.1596	likely_benign	0.2472	benign	-0.171	Destabilizing	0.996	D	0.428	neutral	None	None	None	None	N
T/S	0.1223	likely_benign	0.1662	benign	-0.544	Destabilizing	0.287	N	0.107	neutral	N	0.493178448	None	None	N
T/V	0.1341	likely_benign	0.1854	benign	-0.168	Destabilizing	0.97	D	0.405	neutral	None	None	None	None	N
T/W	0.6369	likely_pathogenic	0.7865	pathogenic	-0.792	Destabilizing	1.0	D	0.633	neutral	None	None	None	None	N
T/Y	0.3602	ambiguous	0.514	ambiguous	-0.509	Destabilizing	0.999	D	0.525	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.