TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18348	55267;55268;55269	chr2:178602360;178602359;178602358	chr2:179467087;179467086;179467085
N2AB	16707	50344;50345;50346	chr2:178602360;178602359;178602358	chr2:179467087;179467086;179467085
N2A	15780	47563;47564;47565	chr2:178602360;178602359;178602358	chr2:179467087;179467086;179467085
N2B	9283	28072;28073;28074	chr2:178602360;178602359;178602358	chr2:179467087;179467086;179467085
Novex-1	9408	28447;28448;28449	chr2:178602360;178602359;178602358	chr2:179467087;179467086;179467085
Novex-2	9475	28648;28649;28650	chr2:178602360;178602359;178602358	chr2:179467087;179467086;179467085
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-21
• Domain position: 77
• Structural Position: 107
• Q(SASA): 0.1402
• 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
R/G	None	None	0.939	D	0.517	0.44	0.550545596621	gnomAD-4.0.0	1.5932E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86159E-06	0	0
R/K	None	None	0.76	N	0.611	0.315	0.371903410333	gnomAD-4.0.0	7.20193E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.56251E-06	0	3.66327E-05

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
R/A	0.9649	likely_pathogenic	0.9695	pathogenic	-1.854	Destabilizing	0.953	D	0.529	neutral	None	None	None	None	N
R/C	0.558	ambiguous	0.5519	ambiguous	-1.806	Destabilizing	0.999	D	0.697	prob.neutral	None	None	None	None	N
R/D	0.9973	likely_pathogenic	0.9972	pathogenic	-0.99	Destabilizing	0.986	D	0.549	neutral	None	None	None	None	N
R/E	0.9587	likely_pathogenic	0.959	pathogenic	-0.781	Destabilizing	0.91	D	0.571	neutral	None	None	None	None	N
R/F	0.9814	likely_pathogenic	0.9767	pathogenic	-1.085	Destabilizing	0.998	D	0.717	prob.delet.	None	None	None	None	N
R/G	0.9624	likely_pathogenic	0.9662	pathogenic	-2.183	Highly Destabilizing	0.939	D	0.517	neutral	D	0.55052789	None	None	N
R/H	0.5285	ambiguous	0.4288	ambiguous	-2.115	Highly Destabilizing	0.993	D	0.557	neutral	None	None	None	None	N
R/I	0.9143	likely_pathogenic	0.9032	pathogenic	-0.907	Destabilizing	0.991	D	0.704	prob.neutral	N	0.508394351	None	None	N
R/K	0.4936	ambiguous	0.4602	ambiguous	-1.28	Destabilizing	0.76	D	0.611	neutral	N	0.495566334	None	None	N
R/L	0.8968	likely_pathogenic	0.896	pathogenic	-0.907	Destabilizing	0.953	D	0.517	neutral	None	None	None	None	N
R/M	0.9378	likely_pathogenic	0.9401	pathogenic	-1.437	Destabilizing	0.999	D	0.597	neutral	None	None	None	None	N
R/N	0.9901	likely_pathogenic	0.989	pathogenic	-1.251	Destabilizing	0.986	D	0.513	neutral	None	None	None	None	N
R/P	0.9985	likely_pathogenic	0.9987	pathogenic	-1.211	Destabilizing	0.993	D	0.624	neutral	None	None	None	None	N
R/Q	0.4254	ambiguous	0.4142	ambiguous	-1.074	Destabilizing	0.386	N	0.449	neutral	None	None	None	None	N
R/S	0.9783	likely_pathogenic	0.979	pathogenic	-2.065	Highly Destabilizing	0.939	D	0.505	neutral	D	0.524519915	None	None	N
R/T	0.9523	likely_pathogenic	0.9524	pathogenic	-1.655	Destabilizing	0.982	D	0.507	neutral	N	0.502403189	None	None	N
R/V	0.9284	likely_pathogenic	0.9285	pathogenic	-1.211	Destabilizing	0.993	D	0.672	neutral	None	None	None	None	N
R/W	0.802	likely_pathogenic	0.764	pathogenic	-0.698	Destabilizing	0.999	D	0.673	neutral	None	None	None	None	N
R/Y	0.9615	likely_pathogenic	0.9503	pathogenic	-0.521	Destabilizing	0.998	D	0.659	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.