TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6859	20800;20801;20802	chr2:178725629;178725628;178725627	chr2:179590356;179590355;179590354
N2AB	6542	19849;19850;19851	chr2:178725629;178725628;178725627	chr2:179590356;179590355;179590354
N2A	5615	17068;17069;17070	chr2:178725629;178725628;178725627	chr2:179590356;179590355;179590354
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-53
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.7031
• 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
K/Q	None	None	0.999	N	0.683	0.391	0.383256108077	gnomAD-4.0.0	1.65812E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.97301E-06	0	0
K/R	None	None	0.884	N	0.255	0.246	0.451023696535	gnomAD-4.0.0	1.65636E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.97016E-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
K/A	0.4186	ambiguous	0.5269	ambiguous	-0.422	Destabilizing	0.998	D	0.601	neutral	None	None	None	None	I
K/C	0.8227	likely_pathogenic	0.8468	pathogenic	-0.409	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	I
K/D	0.6441	likely_pathogenic	0.7819	pathogenic	0.276	Stabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	I
K/E	0.2635	likely_benign	0.4197	ambiguous	0.342	Stabilizing	0.996	D	0.593	neutral	N	0.485897047	None	None	I
K/F	0.8118	likely_pathogenic	0.8579	pathogenic	-0.413	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	I
K/G	0.5193	ambiguous	0.5978	pathogenic	-0.696	Destabilizing	1.0	D	0.55	neutral	None	None	None	None	I
K/H	0.3623	ambiguous	0.4066	ambiguous	-0.959	Destabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	I
K/I	0.4856	ambiguous	0.5998	pathogenic	0.25	Stabilizing	1.0	D	0.725	prob.delet.	N	0.509837426	None	None	I
K/L	0.4849	ambiguous	0.5933	pathogenic	0.25	Stabilizing	1.0	D	0.55	neutral	None	None	None	None	I
K/M	0.3505	ambiguous	0.4698	ambiguous	0.059	Stabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	I
K/N	0.5109	ambiguous	0.6433	pathogenic	-0.03	Destabilizing	0.999	D	0.693	prob.neutral	N	0.506838912	None	None	I
K/P	0.5151	ambiguous	0.6135	pathogenic	0.055	Stabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	I
K/Q	0.1675	likely_benign	0.2181	benign	-0.115	Destabilizing	0.999	D	0.683	prob.neutral	N	0.488948467	None	None	I
K/R	0.0911	likely_benign	0.0889	benign	-0.214	Destabilizing	0.884	D	0.255	neutral	N	0.489455446	None	None	I
K/S	0.4796	ambiguous	0.5869	pathogenic	-0.664	Destabilizing	0.998	D	0.639	neutral	None	None	None	None	I
K/T	0.2491	likely_benign	0.3512	ambiguous	-0.408	Destabilizing	0.999	D	0.663	neutral	N	0.496861732	None	None	I
K/V	0.4464	ambiguous	0.5502	ambiguous	0.055	Stabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
K/W	0.8212	likely_pathogenic	0.8521	pathogenic	-0.334	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	I
K/Y	0.6711	likely_pathogenic	0.7432	pathogenic	-0.023	Destabilizing	1.0	D	0.699	prob.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.