TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23907	71944;71945;71946	chr2:178574413;178574412;178574411	chr2:179439140;179439139;179439138
N2AB	22266	67021;67022;67023	chr2:178574413;178574412;178574411	chr2:179439140;179439139;179439138
N2A	21339	64240;64241;64242	chr2:178574413;178574412;178574411	chr2:179439140;179439139;179439138
N2B	14842	44749;44750;44751	chr2:178574413;178574412;178574411	chr2:179439140;179439139;179439138
Novex-1	14967	45124;45125;45126	chr2:178574413;178574412;178574411	chr2:179439140;179439139;179439138
Novex-2	15034	45325;45326;45327	chr2:178574413;178574412;178574411	chr2:179439140;179439139;179439138
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-61
• Domain position: 82
• Structural Position: 114
• Q(SASA): 0.527
• 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
A/T	rs1309139547	-0.417	0.977	N	0.74	0.385	0.301455362545	gnomAD-2.1.1	3.19E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	6.48E-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
A/C	0.8164	likely_pathogenic	0.7933	pathogenic	-0.832	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	I
A/D	0.9805	likely_pathogenic	0.9799	pathogenic	-0.903	Destabilizing	0.999	D	0.841	deleterious	None	None	None	None	I
A/E	0.9569	likely_pathogenic	0.9539	pathogenic	-1.064	Destabilizing	0.997	D	0.794	deleterious	N	0.498271678	None	None	I
A/F	0.9011	likely_pathogenic	0.869	pathogenic	-1.029	Destabilizing	0.998	D	0.863	deleterious	None	None	None	None	I
A/G	0.4224	ambiguous	0.4305	ambiguous	-0.473	Destabilizing	0.989	D	0.639	neutral	N	0.491928575	None	None	I
A/H	0.9738	likely_pathogenic	0.9646	pathogenic	-0.426	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	I
A/I	0.6557	likely_pathogenic	0.6662	pathogenic	-0.497	Destabilizing	0.966	D	0.717	prob.delet.	None	None	None	None	I
A/K	0.9829	likely_pathogenic	0.9791	pathogenic	-0.858	Destabilizing	0.998	D	0.794	deleterious	None	None	None	None	I
A/L	0.6971	likely_pathogenic	0.6873	pathogenic	-0.497	Destabilizing	0.966	D	0.579	neutral	None	None	None	None	I
A/M	0.7523	likely_pathogenic	0.7335	pathogenic	-0.479	Destabilizing	0.999	D	0.801	deleterious	None	None	None	None	I
A/N	0.9453	likely_pathogenic	0.937	pathogenic	-0.515	Destabilizing	0.999	D	0.86	deleterious	None	None	None	None	I
A/P	0.9646	likely_pathogenic	0.9672	pathogenic	-0.441	Destabilizing	0.999	D	0.798	deleterious	N	0.519164317	None	None	I
A/Q	0.9394	likely_pathogenic	0.9248	pathogenic	-0.849	Destabilizing	0.999	D	0.81	deleterious	None	None	None	None	I
A/R	0.9502	likely_pathogenic	0.9356	pathogenic	-0.267	Destabilizing	0.998	D	0.811	deleterious	None	None	None	None	I
A/S	0.3252	likely_benign	0.3129	benign	-0.667	Destabilizing	0.989	D	0.629	neutral	N	0.474700147	None	None	I
A/T	0.5601	ambiguous	0.5866	pathogenic	-0.759	Destabilizing	0.977	D	0.74	deleterious	N	0.513377419	None	None	I
A/V	0.3008	likely_benign	0.2943	benign	-0.441	Destabilizing	0.235	N	0.447	neutral	N	0.46787941	None	None	I
A/W	0.9885	likely_pathogenic	0.9836	pathogenic	-1.137	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	I
A/Y	0.953	likely_pathogenic	0.9371	pathogenic	-0.823	Destabilizing	0.999	D	0.863	deleterious	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.