TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32891	98896;98897;98898	chr2:178539394;178539393;178539392	chr2:179404121;179404120;179404119
N2AB	31250	93973;93974;93975	chr2:178539394;178539393;178539392	chr2:179404121;179404120;179404119
N2A	30323	91192;91193;91194	chr2:178539394;178539393;178539392	chr2:179404121;179404120;179404119
N2B	23826	71701;71702;71703	chr2:178539394;178539393;178539392	chr2:179404121;179404120;179404119
Novex-1	23951	72076;72077;72078	chr2:178539394;178539393;178539392	chr2:179404121;179404120;179404119
Novex-2	24018	72277;72278;72279	chr2:178539394;178539393;178539392	chr2:179404121;179404120;179404119
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: Fn3-127
• Domain position: 97
• Structural Position: 131
• Q(SASA): 0.4944
• 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/E	rs768773826	None	0.997	N	0.693	0.253	0.239901079897	gnomAD-4.0.0	3.19482E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.74841E-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	0.692	likely_pathogenic	0.6626	pathogenic	-0.401	Destabilizing	0.998	D	0.721	deleterious	None	None	None	None	N
K/C	0.8579	likely_pathogenic	0.8347	pathogenic	-0.418	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
K/D	0.9357	likely_pathogenic	0.9286	pathogenic	-0.313	Destabilizing	0.999	D	0.734	deleterious	None	None	None	None	N
K/E	0.5003	ambiguous	0.4877	ambiguous	-0.203	Destabilizing	0.997	D	0.693	prob.delet.	N	0.46736683	None	None	N
K/F	0.9468	likely_pathogenic	0.9376	pathogenic	0.009	Stabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
K/G	0.8112	likely_pathogenic	0.7788	pathogenic	-0.783	Destabilizing	0.999	D	0.689	prob.delet.	None	None	None	None	N
K/H	0.6246	likely_pathogenic	0.5889	pathogenic	-1.217	Destabilizing	1.0	D	0.622	neutral	None	None	None	None	N
K/I	0.6076	likely_pathogenic	0.6074	pathogenic	0.591	Stabilizing	0.999	D	0.746	deleterious	N	0.450853041	None	None	N
K/L	0.6792	likely_pathogenic	0.653	pathogenic	0.591	Stabilizing	0.999	D	0.689	prob.delet.	None	None	None	None	N
K/M	0.5354	ambiguous	0.5132	ambiguous	0.414	Stabilizing	1.0	D	0.617	neutral	None	None	None	None	N
K/N	0.854	likely_pathogenic	0.842	pathogenic	-0.52	Destabilizing	0.999	D	0.705	prob.delet.	N	0.470313649	None	None	N
K/P	0.9717	likely_pathogenic	0.9679	pathogenic	0.291	Stabilizing	0.999	D	0.707	prob.delet.	None	None	None	None	N
K/Q	0.2527	likely_benign	0.2376	benign	-0.547	Destabilizing	0.999	D	0.74	deleterious	N	0.491627769	None	None	N
K/R	0.0963	likely_benign	0.0927	benign	-0.796	Destabilizing	0.997	D	0.651	prob.neutral	N	0.452338662	None	None	N
K/S	0.8004	likely_pathogenic	0.7711	pathogenic	-1.054	Destabilizing	0.998	D	0.735	deleterious	None	None	None	None	N
K/T	0.4708	ambiguous	0.4627	ambiguous	-0.745	Destabilizing	0.999	D	0.685	prob.delet.	N	0.446886114	None	None	N
K/V	0.4994	ambiguous	0.4927	ambiguous	0.291	Stabilizing	0.999	D	0.744	deleterious	None	None	None	None	N
K/W	0.9562	likely_pathogenic	0.9413	pathogenic	0.066	Stabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
K/Y	0.9002	likely_pathogenic	0.885	pathogenic	0.344	Stabilizing	1.0	D	0.729	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.