TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33297	100114;100115;100116	chr2:178537220;178537219;178537218	chr2:179401947;179401946;179401945
N2AB	31656	95191;95192;95193	chr2:178537220;178537219;178537218	chr2:179401947;179401946;179401945
N2A	30729	92410;92411;92412	chr2:178537220;178537219;178537218	chr2:179401947;179401946;179401945
N2B	24232	72919;72920;72921	chr2:178537220;178537219;178537218	chr2:179401947;179401946;179401945
Novex-1	24357	73294;73295;73296	chr2:178537220;178537219;178537218	chr2:179401947;179401946;179401945
Novex-2	24424	73495;73496;73497	chr2:178537220;178537219;178537218	chr2:179401947;179401946;179401945
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-130
• Domain position: 8
• Structural Position: 8
• Q(SASA): 0.7293
• 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
P/L	rs369205591	-0.168	0.998	N	0.734	0.441	None	gnomAD-2.1.1	8.17E-06	None	None	None	None	I	None	0	2.94E-05	None	0	0	None	0	None	0	9.02E-06	0
P/L	rs369205591	-0.168	0.998	N	0.734	0.441	None	gnomAD-4.0.0	1.61869E-06	None	None	None	None	I	None	0	2.31653E-05	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
P/A	0.2562	likely_benign	0.2611	benign	-0.519	Destabilizing	0.984	D	0.688	prob.neutral	N	0.51656697	None	None	I
P/C	0.83	likely_pathogenic	0.8567	pathogenic	-0.787	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
P/D	0.6065	likely_pathogenic	0.579	pathogenic	-0.147	Destabilizing	0.998	D	0.753	deleterious	None	None	None	None	I
P/E	0.4896	ambiguous	0.4651	ambiguous	-0.234	Destabilizing	0.998	D	0.762	deleterious	None	None	None	None	I
P/F	0.8604	likely_pathogenic	0.8759	pathogenic	-0.58	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	I
P/G	0.6483	likely_pathogenic	0.6313	pathogenic	-0.664	Destabilizing	0.994	D	0.731	prob.delet.	None	None	None	None	I
P/H	0.4873	ambiguous	0.5055	ambiguous	-0.083	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
P/I	0.7289	likely_pathogenic	0.7513	pathogenic	-0.276	Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	I
P/K	0.5974	likely_pathogenic	0.5844	pathogenic	-0.501	Destabilizing	0.998	D	0.756	deleterious	None	None	None	None	I
P/L	0.4012	ambiguous	0.4339	ambiguous	-0.276	Destabilizing	0.998	D	0.734	prob.delet.	N	0.494113713	None	None	I
P/M	0.6965	likely_pathogenic	0.7231	pathogenic	-0.508	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	I
P/N	0.5669	likely_pathogenic	0.5483	ambiguous	-0.341	Destabilizing	0.998	D	0.746	deleterious	None	None	None	None	I
P/Q	0.3843	ambiguous	0.3944	ambiguous	-0.523	Destabilizing	0.999	D	0.729	prob.delet.	N	0.504249613	None	None	I
P/R	0.481	ambiguous	0.4866	ambiguous	-0.013	Destabilizing	0.999	D	0.748	deleterious	N	0.517327439	None	None	I
P/S	0.3608	ambiguous	0.3529	ambiguous	-0.743	Destabilizing	0.79	D	0.383	neutral	N	0.513453098	None	None	I
P/T	0.3267	likely_benign	0.3225	benign	-0.723	Destabilizing	0.995	D	0.765	deleterious	N	0.513453098	None	None	I
P/V	0.5901	likely_pathogenic	0.6098	pathogenic	-0.323	Destabilizing	0.998	D	0.745	deleterious	None	None	None	None	I
P/W	0.9436	likely_pathogenic	0.9528	pathogenic	-0.651	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	I
P/Y	0.817	likely_pathogenic	0.8318	pathogenic	-0.376	Destabilizing	1.0	D	0.754	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.