TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23486	70681;70682;70683	chr2:178575676;178575675;178575674	chr2:179440403;179440402;179440401
N2AB	21845	65758;65759;65760	chr2:178575676;178575675;178575674	chr2:179440403;179440402;179440401
N2A	20918	62977;62978;62979	chr2:178575676;178575675;178575674	chr2:179440403;179440402;179440401
N2B	14421	43486;43487;43488	chr2:178575676;178575675;178575674	chr2:179440403;179440402;179440401
Novex-1	14546	43861;43862;43863	chr2:178575676;178575675;178575674	chr2:179440403;179440402;179440401
Novex-2	14613	44062;44063;44064	chr2:178575676;178575675;178575674	chr2:179440403;179440402;179440401
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-58
• Domain position: 52
• Structural Position: 69
• Q(SASA): 0.1539
• 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
T/I	rs774575929	-0.084	0.497	N	0.621	0.163	0.319114376414	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	2.9E-05	None	0	5.59E-05	None	0	None	0	0	0
T/I	rs774575929	-0.084	0.497	N	0.621	0.163	0.319114376414	gnomAD-4.0.0	2.05284E-06	None	None	None	None	N	None	0	2.23634E-05	None	0	5.04566E-05	None	0	0	0	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
T/A	0.0784	likely_benign	0.0757	benign	-1.004	Destabilizing	0.055	N	0.453	neutral	N	0.475424245	None	None	N
T/C	0.4515	ambiguous	0.4257	ambiguous	-0.531	Destabilizing	0.909	D	0.617	neutral	None	None	None	None	N
T/D	0.5234	ambiguous	0.5072	ambiguous	-0.126	Destabilizing	0.157	N	0.555	neutral	None	None	None	None	N
T/E	0.5869	likely_pathogenic	0.5873	pathogenic	-0.085	Destabilizing	0.157	N	0.548	neutral	None	None	None	None	N
T/F	0.4157	ambiguous	0.4478	ambiguous	-1.03	Destabilizing	0.726	D	0.678	prob.neutral	None	None	None	None	N
T/G	0.298	likely_benign	0.2696	benign	-1.299	Destabilizing	0.157	N	0.577	neutral	None	None	None	None	N
T/H	0.5135	ambiguous	0.5106	ambiguous	-1.504	Destabilizing	0.909	D	0.679	prob.neutral	None	None	None	None	N
T/I	0.2721	likely_benign	0.2955	benign	-0.297	Destabilizing	0.497	N	0.621	neutral	N	0.510998256	None	None	N
T/K	0.6432	likely_pathogenic	0.629	pathogenic	-0.669	Destabilizing	0.157	N	0.556	neutral	None	None	None	None	N
T/L	0.1721	likely_benign	0.1748	benign	-0.297	Destabilizing	0.272	N	0.551	neutral	None	None	None	None	N
T/M	0.125	likely_benign	0.1334	benign	-0.059	Destabilizing	0.968	D	0.615	neutral	None	None	None	None	N
T/N	0.1957	likely_benign	0.194	benign	-0.734	Destabilizing	0.331	N	0.569	neutral	N	0.462222874	None	None	N
T/P	0.7639	likely_pathogenic	0.7529	pathogenic	-0.5	Destabilizing	0.001	N	0.3	neutral	N	0.478627394	None	None	N
T/Q	0.4805	ambiguous	0.4723	ambiguous	-0.785	Destabilizing	0.567	D	0.625	neutral	None	None	None	None	N
T/R	0.5816	likely_pathogenic	0.5704	pathogenic	-0.536	Destabilizing	0.567	D	0.625	neutral	None	None	None	None	N
T/S	0.1096	likely_benign	0.1006	benign	-1.059	Destabilizing	0.001	N	0.215	neutral	N	0.447677496	None	None	N
T/V	0.1675	likely_benign	0.1779	benign	-0.5	Destabilizing	0.272	N	0.527	neutral	None	None	None	None	N
T/W	0.8666	likely_pathogenic	0.8758	pathogenic	-0.976	Destabilizing	0.968	D	0.685	prob.neutral	None	None	None	None	N
T/Y	0.5766	likely_pathogenic	0.5854	pathogenic	-0.728	Destabilizing	0.726	D	0.68	prob.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.