TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7612	23059;23060;23061	chr2:178721185;178721184;178721183	chr2:179585912;179585911;179585910
N2AB	7295	22108;22109;22110	chr2:178721185;178721184;178721183	chr2:179585912;179585911;179585910
N2A	6368	19327;19328;19329	chr2:178721185;178721184;178721183	chr2:179585912;179585911;179585910
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: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-61
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.4777
• 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	rs1553908654	0.318	0.992	N	0.427	0.188	0.370608029945	gnomAD-2.1.1	4.15E-06	None	None	None	None	N	None	0	2.98E-05	None	0	0	None	0	None	0	0	0
K/E	rs1553908654	0.318	0.992	N	0.427	0.188	0.370608029945	gnomAD-4.0.0	6.9122E-07	None	None	None	None	N	None	0	2.28165E-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
K/A	0.7596	likely_pathogenic	0.6123	pathogenic	-0.331	Destabilizing	0.998	D	0.551	neutral	None	None	None	None	N
K/C	0.9176	likely_pathogenic	0.8664	pathogenic	-0.429	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
K/D	0.904	likely_pathogenic	0.7963	pathogenic	-0.007	Destabilizing	0.999	D	0.718	prob.delet.	None	None	None	None	N
K/E	0.4632	ambiguous	0.2972	benign	0.099	Stabilizing	0.992	D	0.427	neutral	N	0.474741959	None	None	N
K/F	0.9461	likely_pathogenic	0.9152	pathogenic	0.011	Stabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
K/G	0.7948	likely_pathogenic	0.6628	pathogenic	-0.677	Destabilizing	0.998	D	0.667	neutral	None	None	None	None	N
K/H	0.522	ambiguous	0.4393	ambiguous	-0.876	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
K/I	0.7596	likely_pathogenic	0.6642	pathogenic	0.556	Stabilizing	0.982	D	0.757	deleterious	None	None	None	None	N
K/L	0.7026	likely_pathogenic	0.5976	pathogenic	0.556	Stabilizing	0.941	D	0.667	neutral	None	None	None	None	N
K/M	0.5704	likely_pathogenic	0.4434	ambiguous	0.208	Stabilizing	0.998	D	0.711	prob.delet.	N	0.486670742	None	None	N
K/N	0.8035	likely_pathogenic	0.6639	pathogenic	-0.329	Destabilizing	0.999	D	0.681	prob.neutral	N	0.484504695	None	None	N
K/P	0.972	likely_pathogenic	0.9455	pathogenic	0.291	Stabilizing	0.999	D	0.757	deleterious	None	None	None	None	N
K/Q	0.213	likely_benign	0.1601	benign	-0.339	Destabilizing	0.994	D	0.655	neutral	N	0.463156742	None	None	N
K/R	0.0987	likely_benign	0.0961	benign	-0.469	Destabilizing	0.987	D	0.395	neutral	N	0.458137711	None	None	N
K/S	0.7659	likely_pathogenic	0.6185	pathogenic	-0.892	Destabilizing	0.998	D	0.541	neutral	None	None	None	None	N
K/T	0.4754	ambiguous	0.3276	benign	-0.589	Destabilizing	0.998	D	0.705	prob.neutral	N	0.489401981	None	None	N
K/V	0.7001	likely_pathogenic	0.5901	pathogenic	0.291	Stabilizing	0.987	D	0.697	prob.neutral	None	None	None	None	N
K/W	0.887	likely_pathogenic	0.8514	pathogenic	0.065	Stabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	N
K/Y	0.8736	likely_pathogenic	0.818	pathogenic	0.342	Stabilizing	0.989	D	0.739	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.