TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32626	98101;98102;98103	chr2:178540290;178540289;178540288	chr2:179405017;179405016;179405015
N2AB	30985	93178;93179;93180	chr2:178540290;178540289;178540288	chr2:179405017;179405016;179405015
N2A	30058	90397;90398;90399	chr2:178540290;178540289;178540288	chr2:179405017;179405016;179405015
N2B	23561	70906;70907;70908	chr2:178540290;178540289;178540288	chr2:179405017;179405016;179405015
Novex-1	23686	71281;71282;71283	chr2:178540290;178540289;178540288	chr2:179405017;179405016;179405015
Novex-2	23753	71482;71483;71484	chr2:178540290;178540289;178540288	chr2:179405017;179405016;179405015
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-126
• Domain position: 27
• Structural Position: 29
• Q(SASA): 0.4567
• 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/N	None	None	0.003	N	0.197	0.201	0.185906805712	gnomAD-4.0.0	6.00165E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.56256E-06	0	0
D/Y	None	None	0.957	N	0.604	0.494	0.489174143269	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-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	0.1374	likely_benign	0.1513	benign	-0.197	Destabilizing	0.505	D	0.493	neutral	N	0.519689523	None	None	N
D/C	0.4475	ambiguous	0.4663	ambiguous	0.154	Stabilizing	0.991	D	0.673	neutral	None	None	None	None	N
D/E	0.0888	likely_benign	0.0907	benign	-0.319	Destabilizing	0.001	N	0.068	neutral	N	0.483824724	None	None	N
D/F	0.3701	ambiguous	0.3926	ambiguous	-0.275	Destabilizing	0.967	D	0.599	neutral	None	None	None	None	N
D/G	0.1611	likely_benign	0.1779	benign	-0.379	Destabilizing	0.338	N	0.414	neutral	N	0.466997011	None	None	N
D/H	0.1978	likely_benign	0.219	benign	-0.183	Destabilizing	0.782	D	0.447	neutral	N	0.501103762	None	None	N
D/I	0.2106	likely_benign	0.2327	benign	0.225	Stabilizing	0.906	D	0.613	neutral	None	None	None	None	N
D/K	0.2165	likely_benign	0.2358	benign	0.372	Stabilizing	0.404	N	0.421	neutral	None	None	None	None	N
D/L	0.2557	likely_benign	0.2813	benign	0.225	Stabilizing	0.826	D	0.57	neutral	None	None	None	None	N
D/M	0.3789	ambiguous	0.4059	ambiguous	0.394	Stabilizing	0.991	D	0.596	neutral	None	None	None	None	N
D/N	0.0924	likely_benign	0.1001	benign	0.158	Stabilizing	0.003	N	0.197	neutral	N	0.486673028	None	None	N
D/P	0.7477	likely_pathogenic	0.7926	pathogenic	0.106	Stabilizing	0.906	D	0.443	neutral	None	None	None	None	N
D/Q	0.2126	likely_benign	0.2259	benign	0.171	Stabilizing	0.404	N	0.389	neutral	None	None	None	None	N
D/R	0.262	likely_benign	0.2888	benign	0.457	Stabilizing	0.826	D	0.504	neutral	None	None	None	None	N
D/S	0.1224	likely_benign	0.1312	benign	0.053	Stabilizing	0.404	N	0.329	neutral	None	None	None	None	N
D/T	0.1598	likely_benign	0.1735	benign	0.19	Stabilizing	0.404	N	0.46	neutral	None	None	None	None	N
D/V	0.1234	likely_benign	0.1389	benign	0.106	Stabilizing	0.879	D	0.571	neutral	N	0.464755285	None	None	N
D/W	0.6939	likely_pathogenic	0.7061	pathogenic	-0.196	Destabilizing	0.991	D	0.691	prob.neutral	None	None	None	None	N
D/Y	0.1217	likely_benign	0.1293	benign	-0.048	Destabilizing	0.957	D	0.604	neutral	N	0.415447648	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.