TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6425	19498;19499;19500	chr2:178728653;178728652;178728651	chr2:179593380;179593379;179593378
N2AB	6108	18547;18548;18549	chr2:178728653;178728652;178728651	chr2:179593380;179593379;179593378
N2A	5181	15766;15767;15768	chr2:178728653;178728652;178728651	chr2:179593380;179593379;179593378
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: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-48
• Domain position: 41
• Structural Position: 58
• Q(SASA): 0.0914
• 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
I/M	rs1306888379	-0.94	0.007	N	0.325	0.169	0.230578612272	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
I/M	rs1306888379	-0.94	0.007	N	0.325	0.169	0.230578612272	gnomAD-4.0.0	6.84414E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99616E-07	0	0
I/V	rs1375877907	-1.43	None	N	0.099	0.099	0.399159426805	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	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
I/A	0.6374	likely_pathogenic	0.5005	ambiguous	-2.288	Highly Destabilizing	0.061	N	0.478	neutral	None	None	None	None	N
I/C	0.9299	likely_pathogenic	0.887	pathogenic	-1.555	Destabilizing	0.94	D	0.61	neutral	None	None	None	None	N
I/D	0.9855	likely_pathogenic	0.9707	pathogenic	-2.892	Highly Destabilizing	0.94	D	0.699	prob.neutral	None	None	None	None	N
I/E	0.9579	likely_pathogenic	0.92	pathogenic	-2.62	Highly Destabilizing	0.593	D	0.671	neutral	None	None	None	None	N
I/F	0.3821	ambiguous	0.2837	benign	-1.452	Destabilizing	0.002	N	0.199	neutral	None	None	None	None	N
I/G	0.9487	likely_pathogenic	0.9109	pathogenic	-2.819	Highly Destabilizing	0.593	D	0.631	neutral	None	None	None	None	N
I/H	0.9343	likely_pathogenic	0.8804	pathogenic	-2.364	Highly Destabilizing	0.94	D	0.643	neutral	None	None	None	None	N
I/K	0.9102	likely_pathogenic	0.8388	pathogenic	-1.799	Destabilizing	0.351	N	0.648	neutral	N	0.507171762	None	None	N
I/L	0.0991	likely_benign	0.0852	benign	-0.721	Destabilizing	None	N	0.079	neutral	N	0.390755139	None	None	N
I/M	0.1192	likely_benign	0.0989	benign	-0.735	Destabilizing	0.007	N	0.325	neutral	N	0.516554083	None	None	N
I/N	0.881	likely_pathogenic	0.786	pathogenic	-2.331	Highly Destabilizing	0.836	D	0.686	prob.neutral	None	None	None	None	N
I/P	0.9464	likely_pathogenic	0.9162	pathogenic	-1.23	Destabilizing	0.94	D	0.695	prob.neutral	None	None	None	None	N
I/Q	0.9068	likely_pathogenic	0.8452	pathogenic	-2.088	Highly Destabilizing	0.836	D	0.675	neutral	None	None	None	None	N
I/R	0.8459	likely_pathogenic	0.7379	pathogenic	-1.786	Destabilizing	0.655	D	0.701	prob.neutral	N	0.507171762	None	None	N
I/S	0.8523	likely_pathogenic	0.734	pathogenic	-2.916	Highly Destabilizing	0.418	N	0.581	neutral	None	None	None	None	N
I/T	0.5977	likely_pathogenic	0.4114	ambiguous	-2.485	Highly Destabilizing	0.183	N	0.515	neutral	N	0.508902827	None	None	N
I/V	0.1156	likely_benign	0.0982	benign	-1.23	Destabilizing	None	N	0.099	neutral	N	0.46645055	None	None	N
I/W	0.9152	likely_pathogenic	0.8723	pathogenic	-1.802	Destabilizing	0.983	D	0.638	neutral	None	None	None	None	N
I/Y	0.8341	likely_pathogenic	0.7621	pathogenic	-1.488	Destabilizing	0.264	N	0.609	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.