TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9531	28816;28817;28818	chr2:178709728;178709727;178709726	chr2:179574455;179574454;179574453
N2AB	9214	27865;27866;27867	chr2:178709728;178709727;178709726	chr2:179574455;179574454;179574453
N2A	8287	25084;25085;25086	chr2:178709728;178709727;178709726	chr2:179574455;179574454;179574453
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: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-81
• Domain position: 39
• Structural Position: 52
• Q(SASA): 0.8125
• Predicted PPI site: I

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
N/T	rs537464608	None	0.959	None	0.311	0.35	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
N/T	rs537464608	None	0.959	None	0.311	0.35	None	gnomAD-4.0.0	2.56183E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.78549E-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
N/A	0.6059	likely_pathogenic	0.5929	pathogenic	-0.336	Destabilizing	0.884	D	0.369	neutral	None	None	None	None	I
N/C	0.6719	likely_pathogenic	0.6841	pathogenic	0.226	Stabilizing	0.999	D	0.475	neutral	None	None	None	None	I
N/D	0.2287	likely_benign	0.222	benign	0.354	Stabilizing	0.015	N	0.15	neutral	None	None	None	None	I
N/E	0.719	likely_pathogenic	0.7249	pathogenic	0.337	Stabilizing	0.759	D	0.341	neutral	None	None	None	None	I
N/F	0.9002	likely_pathogenic	0.8837	pathogenic	-0.718	Destabilizing	0.997	D	0.427	neutral	None	None	None	None	I
N/G	0.4046	ambiguous	0.3695	ambiguous	-0.512	Destabilizing	0.02	N	0.153	neutral	None	None	None	None	I
N/H	0.2758	likely_benign	0.2805	benign	-0.441	Destabilizing	0.996	D	0.349	neutral	None	None	None	None	I
N/I	0.7535	likely_pathogenic	0.7423	pathogenic	0.042	Stabilizing	0.996	D	0.425	neutral	None	None	None	None	I
N/K	0.7475	likely_pathogenic	0.7668	pathogenic	0.145	Stabilizing	0.959	D	0.327	neutral	None	None	None	None	I
N/L	0.6679	likely_pathogenic	0.6615	pathogenic	0.042	Stabilizing	0.991	D	0.419	neutral	None	None	None	None	I
N/M	0.7478	likely_pathogenic	0.7383	pathogenic	0.167	Stabilizing	0.999	D	0.402	neutral	None	None	None	None	I
N/P	0.9591	likely_pathogenic	0.9508	pathogenic	-0.057	Destabilizing	0.997	D	0.402	neutral	None	None	None	None	I
N/Q	0.6786	likely_pathogenic	0.6897	pathogenic	-0.267	Destabilizing	0.991	D	0.329	neutral	None	None	None	None	I
N/R	0.7377	likely_pathogenic	0.7414	pathogenic	0.175	Stabilizing	0.991	D	0.323	neutral	None	None	None	None	I
N/S	0.1505	likely_benign	0.1479	benign	-0.154	Destabilizing	0.826	D	0.393	neutral	None	None	None	None	I
N/T	0.4217	ambiguous	0.4225	ambiguous	-0.017	Destabilizing	0.959	D	0.311	neutral	None	None	None	None	I
N/V	0.7613	likely_pathogenic	0.7568	pathogenic	-0.057	Destabilizing	0.997	D	0.428	neutral	None	None	None	None	I
N/W	0.9644	likely_pathogenic	0.9566	pathogenic	-0.726	Destabilizing	0.999	D	0.573	neutral	None	None	None	None	I
N/Y	0.4764	ambiguous	0.4629	ambiguous	-0.439	Destabilizing	0.996	D	0.395	neutral	None	None	None	None	I

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.