TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9337	28234;28235;28236	chr2:178711227;178711226;178711225	chr2:179575954;179575953;179575952
N2AB	9020	27283;27284;27285	chr2:178711227;178711226;178711225	chr2:179575954;179575953;179575952
N2A	8093	24502;24503;24504	chr2:178711227;178711226;178711225	chr2:179575954;179575953;179575952
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: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-79
• Domain position: 37
• Structural Position: 51
• Q(SASA): 0.6162
• 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
D/E	rs757848062	-0.134	0.998	None	0.434	0.354	0.0297737177859	gnomAD-2.1.1	4.01E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
D/E	rs757848062	-0.134	0.998	None	0.434	0.354	0.0297737177859	gnomAD-4.0.0	6.84175E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.65645E-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
D/A	0.5411	ambiguous	0.6283	pathogenic	-0.588	Destabilizing	0.999	D	0.593	neutral	None	None	None	None	N
D/C	0.9365	likely_pathogenic	0.9439	pathogenic	-0.222	Destabilizing	1.0	D	0.641	neutral	None	None	None	None	N
D/E	0.4644	ambiguous	0.5654	pathogenic	-0.381	Destabilizing	0.998	D	0.434	neutral	None	None	None	None	N
D/F	0.9157	likely_pathogenic	0.9361	pathogenic	-0.23	Destabilizing	1.0	D	0.635	neutral	None	None	None	None	N
D/G	0.358	ambiguous	0.4275	ambiguous	-0.845	Destabilizing	0.996	D	0.62	neutral	None	None	None	None	N
D/H	0.7692	likely_pathogenic	0.8167	pathogenic	-0.143	Destabilizing	1.0	D	0.627	neutral	None	None	None	None	N
D/I	0.9016	likely_pathogenic	0.9262	pathogenic	0.067	Stabilizing	1.0	D	0.67	neutral	None	None	None	None	N
D/K	0.8657	likely_pathogenic	0.9084	pathogenic	0.002	Stabilizing	0.999	D	0.647	neutral	None	None	None	None	N
D/L	0.8569	likely_pathogenic	0.8966	pathogenic	0.067	Stabilizing	1.0	D	0.649	neutral	None	None	None	None	N
D/M	0.9357	likely_pathogenic	0.9509	pathogenic	0.28	Stabilizing	1.0	D	0.63	neutral	None	None	None	None	N
D/N	0.1665	likely_benign	0.1891	benign	-0.448	Destabilizing	0.884	D	0.336	neutral	None	None	None	None	N
D/P	0.9938	likely_pathogenic	0.9958	pathogenic	-0.129	Destabilizing	1.0	D	0.658	neutral	None	None	None	None	N
D/Q	0.7986	likely_pathogenic	0.863	pathogenic	-0.368	Destabilizing	1.0	D	0.64	neutral	None	None	None	None	N
D/R	0.8575	likely_pathogenic	0.904	pathogenic	0.271	Stabilizing	1.0	D	0.63	neutral	None	None	None	None	N
D/S	0.3562	ambiguous	0.4134	ambiguous	-0.594	Destabilizing	0.997	D	0.582	neutral	None	None	None	None	N
D/T	0.7572	likely_pathogenic	0.8011	pathogenic	-0.381	Destabilizing	0.999	D	0.653	neutral	None	None	None	None	N
D/V	0.7384	likely_pathogenic	0.8	pathogenic	-0.129	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	N
D/W	0.9776	likely_pathogenic	0.9837	pathogenic	0.019	Stabilizing	1.0	D	0.651	neutral	None	None	None	None	N
D/Y	0.5559	ambiguous	0.6449	pathogenic	0.027	Stabilizing	1.0	D	0.628	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.