TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19047	57364;57365;57366	chr2:178598031;178598030;178598029	chr2:179462758;179462757;179462756
N2AB	17406	52441;52442;52443	chr2:178598031;178598030;178598029	chr2:179462758;179462757;179462756
N2A	16479	49660;49661;49662	chr2:178598031;178598030;178598029	chr2:179462758;179462757;179462756
N2B	9982	30169;30170;30171	chr2:178598031;178598030;178598029	chr2:179462758;179462757;179462756
Novex-1	10107	30544;30545;30546	chr2:178598031;178598030;178598029	chr2:179462758;179462757;179462756
Novex-2	10174	30745;30746;30747	chr2:178598031;178598030;178598029	chr2:179462758;179462757;179462756
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-26
• Domain position: 60
• Structural Position: 90
• Q(SASA): 0.4226
• 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
K/N	rs758155786	-0.529	1.0	N	0.746	0.304	0.141422826196	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
K/N	rs758155786	-0.529	1.0	N	0.746	0.304	0.141422826196	gnomAD-4.0.0	1.59283E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86036E-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	0.7003	likely_pathogenic	0.6152	pathogenic	-0.445	Destabilizing	0.999	D	0.675	prob.neutral	None	None	None	None	N
K/C	0.7836	likely_pathogenic	0.7331	pathogenic	-0.561	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
K/D	0.9121	likely_pathogenic	0.8571	pathogenic	-0.078	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
K/E	0.5765	likely_pathogenic	0.4357	ambiguous	0.037	Stabilizing	0.999	D	0.586	neutral	N	0.420392107	None	None	N
K/F	0.9268	likely_pathogenic	0.8854	pathogenic	-0.103	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
K/G	0.7868	likely_pathogenic	0.7105	pathogenic	-0.792	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
K/H	0.4032	ambiguous	0.3607	ambiguous	-0.958	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
K/I	0.7723	likely_pathogenic	0.6602	pathogenic	0.448	Stabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
K/L	0.7471	likely_pathogenic	0.6632	pathogenic	0.448	Stabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
K/M	0.568	likely_pathogenic	0.4523	ambiguous	0.062	Stabilizing	1.0	D	0.777	deleterious	N	0.510478181	None	None	N
K/N	0.7575	likely_pathogenic	0.6733	pathogenic	-0.464	Destabilizing	1.0	D	0.746	deleterious	N	0.481136709	None	None	N
K/P	0.9819	likely_pathogenic	0.9773	pathogenic	0.18	Stabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
K/Q	0.2482	likely_benign	0.2075	benign	-0.459	Destabilizing	1.0	D	0.719	prob.delet.	N	0.477133612	None	None	N
K/R	0.0842	likely_benign	0.0815	benign	-0.459	Destabilizing	0.999	D	0.562	neutral	N	0.469399563	None	None	N
K/S	0.7109	likely_pathogenic	0.6255	pathogenic	-1.025	Destabilizing	0.999	D	0.664	neutral	None	None	None	None	N
K/T	0.4322	ambiguous	0.3236	benign	-0.711	Destabilizing	1.0	D	0.764	deleterious	N	0.447442636	None	None	N
K/V	0.6682	likely_pathogenic	0.5445	ambiguous	0.18	Stabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
K/W	0.903	likely_pathogenic	0.8618	pathogenic	-0.048	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
K/Y	0.8347	likely_pathogenic	0.7708	pathogenic	0.234	Stabilizing	1.0	D	0.811	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.