TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32512	97759;97760;97761	chr2:178541543;178541542;178541541	chr2:179406270;179406269;179406268
N2AB	30871	92836;92837;92838	chr2:178541543;178541542;178541541	chr2:179406270;179406269;179406268
N2A	29944	90055;90056;90057	chr2:178541543;178541542;178541541	chr2:179406270;179406269;179406268
N2B	23447	70564;70565;70566	chr2:178541543;178541542;178541541	chr2:179406270;179406269;179406268
Novex-1	23572	70939;70940;70941	chr2:178541543;178541542;178541541	chr2:179406270;179406269;179406268
Novex-2	23639	71140;71141;71142	chr2:178541543;178541542;178541541	chr2:179406270;179406269;179406268
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: Fn3-125
• Domain position: 14
• Structural Position: 16
• Q(SASA): 0.1876
• 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	rs1220964715	None	0.999	N	0.641	0.461	0.635165634531	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	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
S/A	0.1774	likely_benign	0.1533	benign	-0.332	Destabilizing	0.973	D	0.446	neutral	N	0.478483193	None	None	N
S/C	0.1617	likely_benign	0.1361	benign	-0.401	Destabilizing	1.0	D	0.58	neutral	N	0.49411153	None	None	N
S/D	0.7672	likely_pathogenic	0.7504	pathogenic	-1.328	Destabilizing	0.996	D	0.545	neutral	None	None	None	None	N
S/E	0.8867	likely_pathogenic	0.8757	pathogenic	-1.334	Destabilizing	0.996	D	0.548	neutral	None	None	None	None	N
S/F	0.5239	ambiguous	0.4825	ambiguous	-0.697	Destabilizing	0.999	D	0.641	neutral	N	0.516790865	None	None	N
S/G	0.1528	likely_benign	0.1315	benign	-0.56	Destabilizing	0.996	D	0.467	neutral	None	None	None	None	N
S/H	0.644	likely_pathogenic	0.6089	pathogenic	-1.249	Destabilizing	1.0	D	0.579	neutral	None	None	None	None	N
S/I	0.6547	likely_pathogenic	0.599	pathogenic	0.16	Stabilizing	0.998	D	0.632	neutral	None	None	None	None	N
S/K	0.9383	likely_pathogenic	0.9273	pathogenic	-0.766	Destabilizing	0.996	D	0.549	neutral	None	None	None	None	N
S/L	0.2572	likely_benign	0.2289	benign	0.16	Stabilizing	0.992	D	0.582	neutral	None	None	None	None	N
S/M	0.4525	ambiguous	0.4121	ambiguous	0.572	Stabilizing	1.0	D	0.582	neutral	None	None	None	None	N
S/N	0.3718	ambiguous	0.327	benign	-0.934	Destabilizing	0.996	D	0.549	neutral	None	None	None	None	N
S/P	0.9279	likely_pathogenic	0.9151	pathogenic	0.03	Stabilizing	0.999	D	0.597	neutral	N	0.487110091	None	None	N
S/Q	0.8007	likely_pathogenic	0.7743	pathogenic	-1.159	Destabilizing	1.0	D	0.59	neutral	None	None	None	None	N
S/R	0.8827	likely_pathogenic	0.8574	pathogenic	-0.598	Destabilizing	0.999	D	0.609	neutral	None	None	None	None	N
S/T	0.1136	likely_benign	0.101	benign	-0.724	Destabilizing	0.333	N	0.241	neutral	N	0.385260813	None	None	N
S/V	0.5782	likely_pathogenic	0.5108	ambiguous	0.03	Stabilizing	0.992	D	0.583	neutral	None	None	None	None	N
S/W	0.6698	likely_pathogenic	0.6395	pathogenic	-0.82	Destabilizing	1.0	D	0.639	neutral	None	None	None	None	N
S/Y	0.4838	ambiguous	0.4533	ambiguous	-0.471	Destabilizing	0.999	D	0.631	neutral	N	0.520407173	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.