TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24259	73000;73001;73002	chr2:178573357;178573356;178573355	chr2:179438084;179438083;179438082
N2AB	22618	68077;68078;68079	chr2:178573357;178573356;178573355	chr2:179438084;179438083;179438082
N2A	21691	65296;65297;65298	chr2:178573357;178573356;178573355	chr2:179438084;179438083;179438082
N2B	15194	45805;45806;45807	chr2:178573357;178573356;178573355	chr2:179438084;179438083;179438082
Novex-1	15319	46180;46181;46182	chr2:178573357;178573356;178573355	chr2:179438084;179438083;179438082
Novex-2	15386	46381;46382;46383	chr2:178573357;178573356;178573355	chr2:179438084;179438083;179438082
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-64
• Domain position: 38
• Structural Position: 40
• Q(SASA): 0.0868
• 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
V/L	None	None	0.9	N	0.301	0.234	0.63781096912	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
V/A	0.6107	likely_pathogenic	0.5614	ambiguous	-2.501	Highly Destabilizing	0.948	D	0.578	neutral	D	0.544604358	None	None	N
V/C	0.9363	likely_pathogenic	0.9169	pathogenic	-1.759	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
V/D	0.9978	likely_pathogenic	0.9972	pathogenic	-3.447	Highly Destabilizing	0.999	D	0.876	deleterious	None	None	None	None	N
V/E	0.9921	likely_pathogenic	0.9902	pathogenic	-3.135	Highly Destabilizing	0.999	D	0.845	deleterious	D	0.556885716	None	None	N
V/F	0.8211	likely_pathogenic	0.7909	pathogenic	-1.472	Destabilizing	0.998	D	0.741	deleterious	None	None	None	None	N
V/G	0.8917	likely_pathogenic	0.8652	pathogenic	-3.064	Highly Destabilizing	0.999	D	0.862	deleterious	D	0.556885716	None	None	N
V/H	0.9974	likely_pathogenic	0.9965	pathogenic	-2.943	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
V/I	0.0771	likely_benign	0.0772	benign	-0.836	Destabilizing	0.246	N	0.18	neutral	None	None	None	None	N
V/K	0.9935	likely_pathogenic	0.9921	pathogenic	-2.07	Highly Destabilizing	0.999	D	0.845	deleterious	None	None	None	None	N
V/L	0.2248	likely_benign	0.2085	benign	-0.836	Destabilizing	0.9	D	0.301	neutral	N	0.470274715	None	None	N
V/M	0.4557	ambiguous	0.4161	ambiguous	-1.074	Destabilizing	0.997	D	0.627	neutral	N	0.512928525	None	None	N
V/N	0.9923	likely_pathogenic	0.9894	pathogenic	-2.788	Highly Destabilizing	0.999	D	0.891	deleterious	None	None	None	None	N
V/P	0.9697	likely_pathogenic	0.971	pathogenic	-1.378	Destabilizing	0.999	D	0.855	deleterious	None	None	None	None	N
V/Q	0.9897	likely_pathogenic	0.9863	pathogenic	-2.423	Highly Destabilizing	0.999	D	0.877	deleterious	None	None	None	None	N
V/R	0.9886	likely_pathogenic	0.9853	pathogenic	-2.166	Highly Destabilizing	0.999	D	0.889	deleterious	None	None	None	None	N
V/S	0.9505	likely_pathogenic	0.9343	pathogenic	-3.201	Highly Destabilizing	0.999	D	0.811	deleterious	None	None	None	None	N
V/T	0.761	likely_pathogenic	0.744	pathogenic	-2.744	Highly Destabilizing	0.992	D	0.584	neutral	None	None	None	None	N
V/W	0.9964	likely_pathogenic	0.9955	pathogenic	-1.987	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
V/Y	0.9891	likely_pathogenic	0.986	pathogenic	-1.749	Destabilizing	0.999	D	0.737	prob.delet.	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.