TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10001	30226;30227;30228	chr2:178704369;178704368;178704367	chr2:179569096;179569095;179569094
N2AB	9684	29275;29276;29277	chr2:178704369;178704368;178704367	chr2:179569096;179569095;179569094
N2A	8757	26494;26495;26496	chr2:178704369;178704368;178704367	chr2:179569096;179569095;179569094
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-85
• Domain position: 13
• Structural Position: 18
• Q(SASA): 0.5087
• 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	rs747230082	0.108	0.949	None	0.512	0.269	0.232513804876	gnomAD-2.1.1	8.03E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	8.85E-06	0
K/N	rs747230082	0.108	0.949	None	0.512	0.269	0.232513804876	gnomAD-4.0.0	3.18227E-06	None	None	None	None	N	None	0	2.28624E-05	None	0	0	None	0	0	2.8582E-06	0	0
K/R	None	None	0.84	None	0.515	0.226	0.300449992093	gnomAD-4.0.0	4.80129E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.25001E-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	0.8494	likely_pathogenic	0.7711	pathogenic	-0.121	Destabilizing	0.775	D	0.57	neutral	None	None	None	None	N
K/C	0.9659	likely_pathogenic	0.9566	pathogenic	-0.307	Destabilizing	0.996	D	0.676	prob.neutral	None	None	None	None	N
K/D	0.9654	likely_pathogenic	0.9425	pathogenic	0.034	Stabilizing	0.961	D	0.536	neutral	None	None	None	None	N
K/E	0.6837	likely_pathogenic	0.5263	ambiguous	0.088	Stabilizing	0.84	D	0.545	neutral	None	None	None	None	N
K/F	0.9784	likely_pathogenic	0.9655	pathogenic	-0.011	Destabilizing	0.923	D	0.649	neutral	None	None	None	None	N
K/G	0.9092	likely_pathogenic	0.8664	pathogenic	-0.404	Destabilizing	0.961	D	0.581	neutral	None	None	None	None	N
K/H	0.7602	likely_pathogenic	0.6971	pathogenic	-0.649	Destabilizing	0.996	D	0.56	neutral	None	None	None	None	N
K/I	0.8544	likely_pathogenic	0.7872	pathogenic	0.57	Stabilizing	0.018	N	0.503	neutral	None	None	None	None	N
K/L	0.7702	likely_pathogenic	0.6828	pathogenic	0.57	Stabilizing	0.372	N	0.598	neutral	None	None	None	None	N
K/M	0.6883	likely_pathogenic	0.5747	pathogenic	0.239	Stabilizing	0.979	D	0.541	neutral	None	None	None	None	N
K/N	0.9102	likely_pathogenic	0.8512	pathogenic	-0.044	Destabilizing	0.949	D	0.512	neutral	None	None	None	None	N
K/P	0.8855	likely_pathogenic	0.8415	pathogenic	0.37	Stabilizing	0.987	D	0.551	neutral	None	None	None	None	N
K/Q	0.4164	ambiguous	0.313	benign	-0.148	Destabilizing	0.983	D	0.55	neutral	None	None	None	None	N
K/R	0.1304	likely_benign	0.115	benign	-0.296	Destabilizing	0.84	D	0.515	neutral	None	None	None	None	N
K/S	0.9117	likely_pathogenic	0.8527	pathogenic	-0.562	Destabilizing	0.633	D	0.525	neutral	None	None	None	None	N
K/T	0.6454	likely_pathogenic	0.5283	ambiguous	-0.335	Destabilizing	0.034	N	0.37	neutral	None	None	None	None	N
K/V	0.8238	likely_pathogenic	0.7564	pathogenic	0.37	Stabilizing	0.372	N	0.589	neutral	None	None	None	None	N
K/W	0.9696	likely_pathogenic	0.9545	pathogenic	0.022	Stabilizing	0.996	D	0.691	prob.neutral	None	None	None	None	N
K/Y	0.9559	likely_pathogenic	0.9336	pathogenic	0.322	Stabilizing	0.961	D	0.632	neutral	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.