TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29711	89356;89357;89358	chr2:178553980;178553979;178553978	chr2:179418707;179418706;179418705
N2AB	28070	84433;84434;84435	chr2:178553980;178553979;178553978	chr2:179418707;179418706;179418705
N2A	27143	81652;81653;81654	chr2:178553980;178553979;178553978	chr2:179418707;179418706;179418705
N2B	20646	62161;62162;62163	chr2:178553980;178553979;178553978	chr2:179418707;179418706;179418705
Novex-1	20771	62536;62537;62538	chr2:178553980;178553979;178553978	chr2:179418707;179418706;179418705
Novex-2	20838	62737;62738;62739	chr2:178553980;178553979;178553978	chr2:179418707;179418706;179418705
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-104
• Domain position: 79
• Structural Position: 111
• Q(SASA): 0.1369
• Predicted PPI site: I

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
V/I	None	None	None	N	0.18	0.097	0.263140351381	gnomAD-4.0.0	1.59482E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43509E-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
V/A	0.3113	likely_benign	0.3236	benign	-1.929	Destabilizing	0.22	N	0.471	neutral	N	0.47578392	None	None	I
V/C	0.7255	likely_pathogenic	0.7689	pathogenic	-1.919	Destabilizing	0.968	D	0.701	prob.neutral	None	None	None	None	I
V/D	0.7754	likely_pathogenic	0.7655	pathogenic	-2.468	Highly Destabilizing	0.89	D	0.803	deleterious	None	None	None	None	I
V/E	0.4067	ambiguous	0.3995	ambiguous	-2.309	Highly Destabilizing	0.667	D	0.726	prob.delet.	N	0.440085094	None	None	I
V/F	0.2485	likely_benign	0.2627	benign	-1.255	Destabilizing	0.396	N	0.724	prob.delet.	None	None	None	None	I
V/G	0.5436	ambiguous	0.5487	ambiguous	-2.383	Highly Destabilizing	0.667	D	0.759	deleterious	N	0.515412698	None	None	I
V/H	0.7465	likely_pathogenic	0.7811	pathogenic	-1.981	Destabilizing	0.968	D	0.793	deleterious	None	None	None	None	I
V/I	0.0662	likely_benign	0.0672	benign	-0.694	Destabilizing	None	N	0.18	neutral	N	0.476389824	None	None	I
V/K	0.5478	ambiguous	0.5627	ambiguous	-1.434	Destabilizing	0.726	D	0.729	prob.delet.	None	None	None	None	I
V/L	0.1817	likely_benign	0.1974	benign	-0.694	Destabilizing	0.001	N	0.261	neutral	N	0.484124804	None	None	I
V/M	0.1339	likely_benign	0.1419	benign	-1.001	Destabilizing	0.396	N	0.56	neutral	None	None	None	None	I
V/N	0.5301	ambiguous	0.548	ambiguous	-1.674	Destabilizing	0.89	D	0.805	deleterious	None	None	None	None	I
V/P	0.982	likely_pathogenic	0.9825	pathogenic	-1.078	Destabilizing	0.89	D	0.759	deleterious	None	None	None	None	I
V/Q	0.4055	ambiguous	0.438	ambiguous	-1.641	Destabilizing	0.89	D	0.755	deleterious	None	None	None	None	I
V/R	0.5472	ambiguous	0.5549	ambiguous	-1.202	Destabilizing	0.726	D	0.807	deleterious	None	None	None	None	I
V/S	0.3934	ambiguous	0.413	ambiguous	-2.293	Highly Destabilizing	0.726	D	0.701	prob.neutral	None	None	None	None	I
V/T	0.2595	likely_benign	0.285	benign	-2.002	Highly Destabilizing	0.272	N	0.517	neutral	None	None	None	None	I
V/W	0.8923	likely_pathogenic	0.9037	pathogenic	-1.625	Destabilizing	0.968	D	0.749	deleterious	None	None	None	None	I
V/Y	0.6577	likely_pathogenic	0.6879	pathogenic	-1.278	Destabilizing	0.726	D	0.736	prob.delet.	None	None	None	None	I

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.