TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19147	57664;57665;57666	chr2:178597643;178597642;178597641	chr2:179462370;179462369;179462368
N2AB	17506	52741;52742;52743	chr2:178597643;178597642;178597641	chr2:179462370;179462369;179462368
N2A	16579	49960;49961;49962	chr2:178597643;178597642;178597641	chr2:179462370;179462369;179462368
N2B	10082	30469;30470;30471	chr2:178597643;178597642;178597641	chr2:179462370;179462369;179462368
Novex-1	10207	30844;30845;30846	chr2:178597643;178597642;178597641	chr2:179462370;179462369;179462368
Novex-2	10274	31045;31046;31047	chr2:178597643;178597642;178597641	chr2:179462370;179462369;179462368
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Ig-117
• Domain position: 53
• Structural Position: 137
• Q(SASA): 0.1061
• 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
S/F	rs1178386765	None	1.0	D	0.78	0.457	0.832794028055	gnomAD-4.0.0	6.8441E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99635E-07	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
S/A	0.099	likely_benign	0.1018	benign	-1.017	Destabilizing	0.997	D	0.52	neutral	N	0.49138628	None	None	N
S/C	0.1901	likely_benign	0.1951	benign	-0.789	Destabilizing	1.0	D	0.753	deleterious	N	0.512262984	None	None	N
S/D	0.9487	likely_pathogenic	0.9565	pathogenic	-1.517	Destabilizing	0.999	D	0.615	neutral	None	None	None	None	N
S/E	0.9303	likely_pathogenic	0.9311	pathogenic	-1.332	Destabilizing	0.999	D	0.609	neutral	None	None	None	None	N
S/F	0.5984	likely_pathogenic	0.6192	pathogenic	-0.846	Destabilizing	1.0	D	0.78	deleterious	D	0.537332	None	None	N
S/G	0.2909	likely_benign	0.3205	benign	-1.391	Destabilizing	0.999	D	0.568	neutral	None	None	None	None	N
S/H	0.7774	likely_pathogenic	0.7781	pathogenic	-1.625	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
S/I	0.5658	likely_pathogenic	0.558	ambiguous	-0.067	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
S/K	0.9802	likely_pathogenic	0.9791	pathogenic	-0.315	Destabilizing	0.999	D	0.618	neutral	None	None	None	None	N
S/L	0.2918	likely_benign	0.2901	benign	-0.067	Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	N
S/M	0.4028	ambiguous	0.3819	ambiguous	-0.177	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
S/N	0.5883	likely_pathogenic	0.5913	pathogenic	-0.954	Destabilizing	0.999	D	0.615	neutral	None	None	None	None	N
S/P	0.992	likely_pathogenic	0.9942	pathogenic	-0.35	Destabilizing	1.0	D	0.718	prob.delet.	N	0.511891795	None	None	N
S/Q	0.8404	likely_pathogenic	0.8285	pathogenic	-0.777	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
S/R	0.9625	likely_pathogenic	0.963	pathogenic	-0.603	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
S/T	0.1747	likely_benign	0.177	benign	-0.667	Destabilizing	0.999	D	0.557	neutral	N	0.481838503	None	None	N
S/V	0.4266	ambiguous	0.432	ambiguous	-0.35	Destabilizing	1.0	D	0.686	prob.neutral	None	None	None	None	N
S/W	0.8027	likely_pathogenic	0.8065	pathogenic	-1.043	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
S/Y	0.5887	likely_pathogenic	0.5972	pathogenic	-0.621	Destabilizing	1.0	D	0.786	deleterious	D	0.537678717	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.