TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8698	26317;26318;26319	chr2:178715094;178715093;178715092	chr2:179579821;179579820;179579819
N2AB	8381	25366;25367;25368	chr2:178715094;178715093;178715092	chr2:179579821;179579820;179579819
N2A	7454	22585;22586;22587	chr2:178715094;178715093;178715092	chr2:179579821;179579820;179579819
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: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-72
• Domain position: 56
• Structural Position: 136
• Q(SASA): 0.1387
• 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/S	rs751582645	-1.713	None	N	0.439	0.089	0.104622674875	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
T/S	rs751582645	-1.713	None	N	0.439	0.089	0.104622674875	gnomAD-4.0.0	1.59141E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02389E-05

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	0.0636	likely_benign	0.0611	benign	-1.106	Destabilizing	None	N	0.361	neutral	N	0.388636688	None	None	N
T/C	0.2908	likely_benign	0.2973	benign	-0.712	Destabilizing	0.863	D	0.772	deleterious	None	None	None	None	N
T/D	0.801	likely_pathogenic	0.7896	pathogenic	-1.456	Destabilizing	0.047	N	0.789	deleterious	None	None	None	None	N
T/E	0.7599	likely_pathogenic	0.7423	pathogenic	-1.237	Destabilizing	0.836	D	0.793	deleterious	None	None	None	None	N
T/F	0.4006	ambiguous	0.3896	ambiguous	-0.709	Destabilizing	0.99	D	0.803	deleterious	None	None	None	None	N
T/G	0.3351	likely_benign	0.3194	benign	-1.548	Destabilizing	0.146	N	0.741	deleterious	None	None	None	None	N
T/H	0.4252	ambiguous	0.4359	ambiguous	-1.622	Destabilizing	0.667	D	0.772	deleterious	None	None	None	None	N
T/I	0.2653	likely_benign	0.243	benign	0.064	Stabilizing	0.309	N	0.798	deleterious	N	0.464462598	None	None	N
T/K	0.672	likely_pathogenic	0.644	pathogenic	-0.378	Destabilizing	0.877	D	0.797	deleterious	None	None	None	None	N
T/L	0.1651	likely_benign	0.1522	benign	0.064	Stabilizing	0.509	D	0.746	deleterious	None	None	None	None	N
T/M	0.1283	likely_benign	0.1268	benign	0.087	Stabilizing	0.973	D	0.783	deleterious	None	None	None	None	N
T/N	0.3024	likely_benign	0.3039	benign	-1.162	Destabilizing	0.036	N	0.751	deleterious	N	0.477181179	None	None	N
T/P	0.6608	likely_pathogenic	0.5851	pathogenic	-0.294	Destabilizing	0.207	N	0.804	deleterious	N	0.483741792	None	None	N
T/Q	0.5376	ambiguous	0.5382	ambiguous	-0.888	Destabilizing	0.431	N	0.811	deleterious	None	None	None	None	N
T/R	0.5499	ambiguous	0.5133	ambiguous	-0.664	Destabilizing	0.993	D	0.809	deleterious	None	None	None	None	N
T/S	0.127	likely_benign	0.1327	benign	-1.401	Destabilizing	None	N	0.439	neutral	N	0.414244421	None	None	N
T/V	0.1586	likely_benign	0.1458	benign	-0.294	Destabilizing	0.011	N	0.451	neutral	None	None	None	None	N
T/W	0.8135	likely_pathogenic	0.8174	pathogenic	-0.88	Destabilizing	0.996	D	0.774	deleterious	None	None	None	None	N
T/Y	0.4182	ambiguous	0.4285	ambiguous	-0.492	Destabilizing	0.957	D	0.805	deleterious	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.