TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30538	91837;91838;91839	chr2:178550226;178550225;178550224	chr2:179414953;179414952;179414951
N2AB	28897	86914;86915;86916	chr2:178550226;178550225;178550224	chr2:179414953;179414952;179414951
N2A	27970	84133;84134;84135	chr2:178550226;178550225;178550224	chr2:179414953;179414952;179414951
N2B	21473	64642;64643;64644	chr2:178550226;178550225;178550224	chr2:179414953;179414952;179414951
Novex-1	21598	65017;65018;65019	chr2:178550226;178550225;178550224	chr2:179414953;179414952;179414951
Novex-2	21665	65218;65219;65220	chr2:178550226;178550225;178550224	chr2:179414953;179414952;179414951
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-149
• Domain position: 7
• Structural Position: 16
• Q(SASA): 0.2446
• 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
I/T	rs1231839154	None	0.324	D	0.391	0.462	0.684537292048	gnomAD-4.0.0	1.20035E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.31252E-06	0	0
I/V	None	None	0.001	N	0.157	0.078	0.340753184043	gnomAD-4.0.0	1.59192E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85938E-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
I/A	0.5124	ambiguous	0.5997	pathogenic	-2.31	Highly Destabilizing	0.004	N	0.186	neutral	None	None	None	None	I
I/C	0.6654	likely_pathogenic	0.7192	pathogenic	-1.587	Destabilizing	0.944	D	0.447	neutral	None	None	None	None	I
I/D	0.9425	likely_pathogenic	0.9625	pathogenic	-2.077	Highly Destabilizing	0.818	D	0.527	neutral	None	None	None	None	I
I/E	0.8473	likely_pathogenic	0.8921	pathogenic	-1.968	Destabilizing	0.818	D	0.54	neutral	None	None	None	None	I
I/F	0.1977	likely_benign	0.2628	benign	-1.435	Destabilizing	0.627	D	0.453	neutral	N	0.467568058	None	None	I
I/G	0.7929	likely_pathogenic	0.8553	pathogenic	-2.749	Highly Destabilizing	0.388	N	0.519	neutral	None	None	None	None	I
I/H	0.741	likely_pathogenic	0.813	pathogenic	-1.97	Destabilizing	0.981	D	0.508	neutral	None	None	None	None	I
I/K	0.6549	likely_pathogenic	0.7133	pathogenic	-1.756	Destabilizing	0.818	D	0.535	neutral	None	None	None	None	I
I/L	0.1031	likely_benign	0.1145	benign	-1.104	Destabilizing	None	N	0.109	neutral	N	0.468528063	None	None	I
I/M	0.1204	likely_benign	0.1356	benign	-0.977	Destabilizing	0.627	D	0.461	neutral	D	0.524133417	None	None	I
I/N	0.6283	likely_pathogenic	0.7029	pathogenic	-1.763	Destabilizing	0.912	D	0.515	neutral	N	0.519716155	None	None	I
I/P	0.9415	likely_pathogenic	0.9588	pathogenic	-1.48	Destabilizing	0.818	D	0.511	neutral	None	None	None	None	I
I/Q	0.6707	likely_pathogenic	0.7366	pathogenic	-1.822	Destabilizing	0.932	D	0.521	neutral	None	None	None	None	I
I/R	0.5844	likely_pathogenic	0.6617	pathogenic	-1.224	Destabilizing	0.818	D	0.512	neutral	None	None	None	None	I
I/S	0.5533	ambiguous	0.6445	pathogenic	-2.463	Highly Destabilizing	0.193	N	0.429	neutral	N	0.489495126	None	None	I
I/T	0.3701	ambiguous	0.432	ambiguous	-2.229	Highly Destabilizing	0.324	N	0.391	neutral	D	0.523439983	None	None	I
I/V	0.0759	likely_benign	0.0824	benign	-1.48	Destabilizing	0.001	N	0.157	neutral	N	0.401740137	None	None	I
I/W	0.8789	likely_pathogenic	0.9197	pathogenic	-1.632	Destabilizing	0.981	D	0.539	neutral	None	None	None	None	I
I/Y	0.6709	likely_pathogenic	0.7492	pathogenic	-1.407	Destabilizing	0.818	D	0.458	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.