TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21920	65983;65984;65985	chr2:178583045;178583044;178583043	chr2:179447772;179447771;179447770
N2AB	20279	61060;61061;61062	chr2:178583045;178583044;178583043	chr2:179447772;179447771;179447770
N2A	19352	58279;58280;58281	chr2:178583045;178583044;178583043	chr2:179447772;179447771;179447770
N2B	12855	38788;38789;38790	chr2:178583045;178583044;178583043	chr2:179447772;179447771;179447770
Novex-1	12980	39163;39164;39165	chr2:178583045;178583044;178583043	chr2:179447772;179447771;179447770
Novex-2	13047	39364;39365;39366	chr2:178583045;178583044;178583043	chr2:179447772;179447771;179447770
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-125
• Domain position: 55
• Structural Position: 137
• Q(SASA): 0.2313
• 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/I	None	None	0.001	N	0.287	0.255	0.26547132957	gnomAD-4.0.0	1.59705E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43868E-05	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	0.1038	likely_benign	0.0953	benign	-0.992	Destabilizing	0.003	N	0.146	neutral	N	0.481884149	None	None	N
T/C	0.3125	likely_benign	0.2914	benign	-0.749	Destabilizing	0.942	D	0.517	neutral	None	None	None	None	N
T/D	0.6055	likely_pathogenic	0.5847	pathogenic	-1.662	Destabilizing	0.273	N	0.437	neutral	None	None	None	None	N
T/E	0.3705	ambiguous	0.3616	ambiguous	-1.482	Destabilizing	0.236	N	0.401	neutral	None	None	None	None	N
T/F	0.2293	likely_benign	0.2163	benign	-0.639	Destabilizing	0.002	N	0.414	neutral	None	None	None	None	N
T/G	0.3184	likely_benign	0.3073	benign	-1.412	Destabilizing	0.134	N	0.431	neutral	None	None	None	None	N
T/H	0.1628	likely_benign	0.1509	benign	-1.685	Destabilizing	0.842	D	0.541	neutral	None	None	None	None	N
T/I	0.1735	likely_benign	0.1551	benign	0.103	Stabilizing	0.001	N	0.287	neutral	N	0.489658271	None	None	N
T/K	0.1157	likely_benign	0.1186	benign	-0.741	Destabilizing	0.236	N	0.396	neutral	None	None	None	None	N
T/L	0.1079	likely_benign	0.0955	benign	0.103	Stabilizing	0.001	N	0.249	neutral	None	None	None	None	N
T/M	0.0983	likely_benign	0.0909	benign	0.212	Stabilizing	0.012	N	0.291	neutral	None	None	None	None	N
T/N	0.1485	likely_benign	0.1461	benign	-1.424	Destabilizing	0.002	N	0.241	neutral	N	0.49048499	None	None	N
T/P	0.5697	likely_pathogenic	0.5296	ambiguous	-0.229	Destabilizing	0.534	D	0.52	neutral	N	0.498804424	None	None	N
T/Q	0.1713	likely_benign	0.1668	benign	-1.196	Destabilizing	0.428	N	0.513	neutral	None	None	None	None	N
T/R	0.0975	likely_benign	0.0975	benign	-0.951	Destabilizing	0.428	N	0.483	neutral	None	None	None	None	N
T/S	0.1038	likely_benign	0.1006	benign	-1.555	Destabilizing	0.009	N	0.235	neutral	N	0.421526337	None	None	N
T/V	0.1398	likely_benign	0.126	benign	-0.229	Destabilizing	0.063	N	0.363	neutral	None	None	None	None	N
T/W	0.5717	likely_pathogenic	0.5594	ambiguous	-0.87	Destabilizing	0.984	D	0.546	neutral	None	None	None	None	N
T/Y	0.2422	likely_benign	0.2354	benign	-0.492	Destabilizing	0.273	N	0.533	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.