TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28596	86011;86012;86013	chr2:178560346;178560345;178560344	chr2:179425073;179425072;179425071
N2AB	26955	81088;81089;81090	chr2:178560346;178560345;178560344	chr2:179425073;179425072;179425071
N2A	26028	78307;78308;78309	chr2:178560346;178560345;178560344	chr2:179425073;179425072;179425071
N2B	19531	58816;58817;58818	chr2:178560346;178560345;178560344	chr2:179425073;179425072;179425071
Novex-1	19656	59191;59192;59193	chr2:178560346;178560345;178560344	chr2:179425073;179425072;179425071
Novex-2	19723	59392;59393;59394	chr2:178560346;178560345;178560344	chr2:179425073;179425072;179425071
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: Fn3-96
• Domain position: 47
• Structural Position: 64
• Q(SASA): 0.6851
• 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
R/K	None	None	0.603	N	0.493	0.235	0.177238962908	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
R/A	0.7458	likely_pathogenic	0.6835	pathogenic	0.055	Stabilizing	0.707	D	0.467	neutral	None	None	None	None	I
R/C	0.2458	likely_benign	0.2014	benign	-0.31	Destabilizing	0.995	D	0.596	neutral	None	None	None	None	I
R/D	0.9169	likely_pathogenic	0.8859	pathogenic	-0.272	Destabilizing	0.981	D	0.516	neutral	None	None	None	None	I
R/E	0.7738	likely_pathogenic	0.7076	pathogenic	-0.223	Destabilizing	0.83	D	0.433	neutral	None	None	None	None	I
R/F	0.7013	likely_pathogenic	0.6699	pathogenic	-0.264	Destabilizing	0.809	D	0.582	neutral	None	None	None	None	I
R/G	0.5574	ambiguous	0.4847	ambiguous	-0.093	Destabilizing	0.928	D	0.42	neutral	N	0.516958649	None	None	I
R/H	0.1339	likely_benign	0.1253	benign	-0.58	Destabilizing	0.995	D	0.463	neutral	None	None	None	None	I
R/I	0.5436	ambiguous	0.4915	ambiguous	0.397	Stabilizing	0.761	D	0.527	neutral	N	0.486283489	None	None	I
R/K	0.2194	likely_benign	0.2046	benign	-0.172	Destabilizing	0.603	D	0.493	neutral	N	0.517478724	None	None	I
R/L	0.4189	ambiguous	0.3698	ambiguous	0.397	Stabilizing	0.007	N	0.44	neutral	None	None	None	None	I
R/M	0.5688	likely_pathogenic	0.5228	ambiguous	-0.098	Destabilizing	0.894	D	0.464	neutral	None	None	None	None	I
R/N	0.8082	likely_pathogenic	0.7685	pathogenic	-0.148	Destabilizing	0.981	D	0.465	neutral	None	None	None	None	I
R/P	0.8788	likely_pathogenic	0.8465	pathogenic	0.301	Stabilizing	0.981	D	0.499	neutral	None	None	None	None	I
R/Q	0.1891	likely_benign	0.1591	benign	-0.159	Destabilizing	0.981	D	0.469	neutral	None	None	None	None	I
R/S	0.7882	likely_pathogenic	0.7408	pathogenic	-0.328	Destabilizing	0.928	D	0.419	neutral	N	0.519228163	None	None	I
R/T	0.6417	likely_pathogenic	0.5789	pathogenic	-0.167	Destabilizing	0.645	D	0.423	neutral	N	0.513323698	None	None	I
R/V	0.6454	likely_pathogenic	0.5811	pathogenic	0.301	Stabilizing	0.547	D	0.495	neutral	None	None	None	None	I
R/W	0.2369	likely_benign	0.2083	benign	-0.451	Destabilizing	0.995	D	0.641	neutral	None	None	None	None	I
R/Y	0.4653	ambiguous	0.4281	ambiguous	-0.034	Destabilizing	0.945	D	0.517	neutral	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.