TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33162	99709;99710;99711	chr2:178537723;178537722;178537721	chr2:179402450;179402449;179402448
N2AB	31521	94786;94787;94788	chr2:178537723;178537722;178537721	chr2:179402450;179402449;179402448
N2A	30594	92005;92006;92007	chr2:178537723;178537722;178537721	chr2:179402450;179402449;179402448
N2B	24097	72514;72515;72516	chr2:178537723;178537722;178537721	chr2:179402450;179402449;179402448
Novex-1	24222	72889;72890;72891	chr2:178537723;178537722;178537721	chr2:179402450;179402449;179402448
Novex-2	24289	73090;73091;73092	chr2:178537723;178537722;178537721	chr2:179402450;179402449;179402448
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-156
• Domain position: 62
• Structural Position: 143
• Q(SASA): 0.1281
• 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	1.0	N	0.717	0.452	0.260735089382	gnomAD-4.0.0	6.84224E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99478E-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
T/A	0.2704	likely_benign	0.2791	benign	-0.999	Destabilizing	0.999	D	0.519	neutral	N	0.457323195	None	None	N
T/C	0.7941	likely_pathogenic	0.7765	pathogenic	-1.188	Destabilizing	1.0	D	0.686	prob.neutral	None	None	None	None	N
T/D	0.9625	likely_pathogenic	0.953	pathogenic	-2.286	Highly Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
T/E	0.947	likely_pathogenic	0.9288	pathogenic	-2.137	Highly Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	N
T/F	0.9613	likely_pathogenic	0.9522	pathogenic	-0.749	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
T/G	0.7208	likely_pathogenic	0.7202	pathogenic	-1.344	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
T/H	0.9567	likely_pathogenic	0.9439	pathogenic	-1.467	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
T/I	0.8075	likely_pathogenic	0.7613	pathogenic	-0.122	Destabilizing	1.0	D	0.717	prob.delet.	N	0.451090656	None	None	N
T/K	0.9426	likely_pathogenic	0.9223	pathogenic	-0.938	Destabilizing	1.0	D	0.733	prob.delet.	N	0.377918262	None	None	N
T/L	0.462	ambiguous	0.4663	ambiguous	-0.122	Destabilizing	1.0	D	0.638	neutral	None	None	None	None	N
T/M	0.3391	likely_benign	0.351	ambiguous	-0.108	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
T/N	0.6859	likely_pathogenic	0.6453	pathogenic	-1.632	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
T/P	0.5862	likely_pathogenic	0.5725	pathogenic	-0.384	Destabilizing	1.0	D	0.716	prob.delet.	N	0.424730774	None	None	N
T/Q	0.9124	likely_pathogenic	0.9017	pathogenic	-1.573	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
T/R	0.92	likely_pathogenic	0.8947	pathogenic	-0.891	Destabilizing	1.0	D	0.726	prob.delet.	N	0.403912784	None	None	N
T/S	0.5048	ambiguous	0.4948	ambiguous	-1.677	Destabilizing	0.998	D	0.538	neutral	N	0.410067965	None	None	N
T/V	0.5572	ambiguous	0.5117	ambiguous	-0.384	Destabilizing	1.0	D	0.612	neutral	None	None	None	None	N
T/W	0.9931	likely_pathogenic	0.9899	pathogenic	-0.947	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
T/Y	0.9743	likely_pathogenic	0.9657	pathogenic	-0.563	Destabilizing	1.0	D	0.749	deleterious	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.