TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31266	94021;94022;94023	chr2:178547830;178547829;178547828	chr2:179412557;179412556;179412555
N2AB	29625	89098;89099;89100	chr2:178547830;178547829;178547828	chr2:179412557;179412556;179412555
N2A	28698	86317;86318;86319	chr2:178547830;178547829;178547828	chr2:179412557;179412556;179412555
N2B	22201	66826;66827;66828	chr2:178547830;178547829;178547828	chr2:179412557;179412556;179412555
Novex-1	22326	67201;67202;67203	chr2:178547830;178547829;178547828	chr2:179412557;179412556;179412555
Novex-2	22393	67402;67403;67404	chr2:178547830;178547829;178547828	chr2:179412557;179412556;179412555
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-151
• Domain position: 49
• Structural Position: 127
• Q(SASA): 0.3398
• 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	None	None	0.999	N	0.639	0.158	0.301789629655	gnomAD-4.0.0	1.59111E-06	None	None	None	None	N	None	0	0	None	0	2.77469E-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	0.0906	likely_benign	0.0905	benign	-0.551	Destabilizing	0.992	D	0.611	neutral	D	0.523994557	None	None	N
T/C	0.452	ambiguous	0.4563	ambiguous	-0.208	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
T/D	0.4683	ambiguous	0.4706	ambiguous	0.257	Stabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
T/E	0.3811	ambiguous	0.3805	ambiguous	0.189	Stabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
T/F	0.3723	ambiguous	0.3639	ambiguous	-1.043	Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	N
T/G	0.2724	likely_benign	0.2917	benign	-0.693	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
T/H	0.3271	likely_benign	0.3175	benign	-1.098	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
T/I	0.2444	likely_benign	0.2386	benign	-0.289	Destabilizing	0.79	D	0.409	neutral	N	0.483566416	None	None	N
T/K	0.2989	likely_benign	0.2814	benign	-0.306	Destabilizing	1.0	D	0.787	deleterious	D	0.531979322	None	None	N
T/L	0.1605	likely_benign	0.16	benign	-0.289	Destabilizing	0.988	D	0.639	neutral	None	None	None	None	N
T/M	0.1199	likely_benign	0.1174	benign	0.077	Stabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
T/N	0.1544	likely_benign	0.155	benign	-0.089	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
T/P	0.285	likely_benign	0.3325	benign	-0.347	Destabilizing	1.0	D	0.788	deleterious	D	0.522765193	None	None	N
T/Q	0.2728	likely_benign	0.2715	benign	-0.345	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
T/R	0.242	likely_benign	0.2333	benign	-0.088	Destabilizing	1.0	D	0.795	deleterious	N	0.482805947	None	None	N
T/S	0.1191	likely_benign	0.1168	benign	-0.35	Destabilizing	0.999	D	0.639	neutral	N	0.486708392	None	None	N
T/V	0.1645	likely_benign	0.1533	benign	-0.347	Destabilizing	0.971	D	0.615	neutral	None	None	None	None	N
T/W	0.7127	likely_pathogenic	0.7221	pathogenic	-0.996	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
T/Y	0.3765	ambiguous	0.366	ambiguous	-0.72	Destabilizing	1.0	D	0.827	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.