TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6712	20359;20360;20361	chr2:178727231;178727230;178727229	chr2:179591958;179591957;179591956
N2AB	6395	19408;19409;19410	chr2:178727231;178727230;178727229	chr2:179591958;179591957;179591956
N2A	5468	16627;16628;16629	chr2:178727231;178727230;178727229	chr2:179591958;179591957;179591956
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: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-51
• Domain position: 46
• Structural Position: 111
• Q(SASA): 0.8383
• 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	None	None	None	N	0.132	0.082	0.101711395817	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	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
D/A	0.111	likely_benign	0.116	benign	-0.041	Destabilizing	None	N	0.145	neutral	N	0.469023056	None	None	N
D/C	0.4981	ambiguous	0.5159	ambiguous	0.144	Stabilizing	0.864	D	0.221	neutral	None	None	None	None	N
D/E	0.0784	likely_benign	0.0759	benign	-0.16	Destabilizing	None	N	0.132	neutral	N	0.429291231	None	None	N
D/F	0.4467	ambiguous	0.4543	ambiguous	-0.184	Destabilizing	0.628	D	0.237	neutral	None	None	None	None	N
D/G	0.0989	likely_benign	0.106	benign	-0.164	Destabilizing	None	N	0.123	neutral	N	0.463075731	None	None	N
D/H	0.1589	likely_benign	0.172	benign	0.182	Stabilizing	0.295	N	0.227	neutral	N	0.500327397	None	None	N
D/I	0.2542	likely_benign	0.2569	benign	0.213	Stabilizing	0.356	N	0.292	neutral	None	None	None	None	N
D/K	0.1512	likely_benign	0.1711	benign	0.522	Stabilizing	0.016	N	0.309	neutral	None	None	None	None	N
D/L	0.2347	likely_benign	0.2508	benign	0.213	Stabilizing	0.072	N	0.301	neutral	None	None	None	None	N
D/M	0.4199	ambiguous	0.4252	ambiguous	0.23	Stabilizing	0.628	D	0.222	neutral	None	None	None	None	N
D/N	0.0808	likely_benign	0.0834	benign	0.373	Stabilizing	0.055	N	0.222	neutral	N	0.458248701	None	None	N
D/P	0.2775	likely_benign	0.3065	benign	0.148	Stabilizing	None	N	0.173	neutral	None	None	None	None	N
D/Q	0.1493	likely_benign	0.1619	benign	0.37	Stabilizing	0.038	N	0.25	neutral	None	None	None	None	N
D/R	0.1829	likely_benign	0.2047	benign	0.627	Stabilizing	0.038	N	0.295	neutral	None	None	None	None	N
D/S	0.0846	likely_benign	0.0903	benign	0.262	Stabilizing	0.016	N	0.233	neutral	None	None	None	None	N
D/T	0.1623	likely_benign	0.1672	benign	0.357	Stabilizing	0.072	N	0.31	neutral	None	None	None	None	N
D/V	0.1593	likely_benign	0.1607	benign	0.148	Stabilizing	0.055	N	0.314	neutral	N	0.495825655	None	None	N
D/W	0.6877	likely_pathogenic	0.7051	pathogenic	-0.147	Destabilizing	0.864	D	0.235	neutral	None	None	None	None	N
D/Y	0.1797	likely_benign	0.1959	benign	0.037	Stabilizing	0.56	D	0.235	neutral	N	0.46988603	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.