TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19242	57949;57950;57951	chr2:178595630;178595629;178595628	chr2:179460357;179460356;179460355
N2AB	17601	53026;53027;53028	chr2:178595630;178595629;178595628	chr2:179460357;179460356;179460355
N2A	16674	50245;50246;50247	chr2:178595630;178595629;178595628	chr2:179460357;179460356;179460355
N2B	10177	30754;30755;30756	chr2:178595630;178595629;178595628	chr2:179460357;179460356;179460355
Novex-1	10302	31129;31130;31131	chr2:178595630;178595629;178595628	chr2:179460357;179460356;179460355
Novex-2	10369	31330;31331;31332	chr2:178595630;178595629;178595628	chr2:179460357;179460356;179460355
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-27
• Domain position: 60
• Structural Position: 90
• Q(SASA): 0.3142
• 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
N/K	rs1201568754	None	0.201	N	0.459	0.124	0.110078149338	gnomAD-4.0.0	6.88921E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.0352E-07	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
N/A	0.3371	likely_benign	0.3413	ambiguous	-0.98	Destabilizing	0.25	N	0.523	neutral	None	None	None	None	N
N/C	0.3118	likely_benign	0.3514	ambiguous	-0.056	Destabilizing	0.947	D	0.738	prob.delet.	None	None	None	None	N
N/D	0.2758	likely_benign	0.2808	benign	-0.841	Destabilizing	0.201	N	0.399	neutral	N	0.490140194	None	None	N
N/E	0.5867	likely_pathogenic	0.578	pathogenic	-0.688	Destabilizing	0.25	N	0.447	neutral	None	None	None	None	N
N/F	0.5875	likely_pathogenic	0.5798	pathogenic	-0.484	Destabilizing	0.826	D	0.761	deleterious	None	None	None	None	N
N/G	0.448	ambiguous	0.4468	ambiguous	-1.369	Destabilizing	0.25	N	0.441	neutral	None	None	None	None	N
N/H	0.1578	likely_benign	0.154	benign	-1.024	Destabilizing	0.781	D	0.571	neutral	N	0.477114969	None	None	N
N/I	0.2948	likely_benign	0.32	benign	0.041	Stabilizing	0.638	D	0.752	deleterious	N	0.496778165	None	None	N
N/K	0.6357	likely_pathogenic	0.6404	pathogenic	-0.435	Destabilizing	0.201	N	0.459	neutral	N	0.453891392	None	None	N
N/L	0.3576	ambiguous	0.3693	ambiguous	0.041	Stabilizing	0.7	D	0.681	prob.neutral	None	None	None	None	N
N/M	0.3421	ambiguous	0.3511	ambiguous	0.379	Stabilizing	0.982	D	0.693	prob.neutral	None	None	None	None	N
N/P	0.9394	likely_pathogenic	0.9453	pathogenic	-0.27	Destabilizing	0.7	D	0.674	neutral	None	None	None	None	N
N/Q	0.5035	ambiguous	0.4825	ambiguous	-0.851	Destabilizing	0.7	D	0.553	neutral	None	None	None	None	N
N/R	0.6982	likely_pathogenic	0.6864	pathogenic	-0.583	Destabilizing	0.7	D	0.529	neutral	None	None	None	None	N
N/S	0.1149	likely_benign	0.1189	benign	-1.093	Destabilizing	0.002	N	0.302	neutral	N	0.410116399	None	None	N
N/T	0.1463	likely_benign	0.1549	benign	-0.749	Destabilizing	0.201	N	0.399	neutral	N	0.437804432	None	None	N
N/V	0.2883	likely_benign	0.3048	benign	-0.27	Destabilizing	0.7	D	0.721	prob.delet.	None	None	None	None	N
N/W	0.83	likely_pathogenic	0.8138	pathogenic	-0.291	Destabilizing	0.982	D	0.689	prob.neutral	None	None	None	None	N
N/Y	0.2118	likely_benign	0.2137	benign	-0.07	Destabilizing	0.781	D	0.714	prob.delet.	N	0.509168672	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.