TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33334	100225;100226;100227	chr2:178537109;178537108;178537107	chr2:179401836;179401835;179401834
N2AB	31693	95302;95303;95304	chr2:178537109;178537108;178537107	chr2:179401836;179401835;179401834
N2A	30766	92521;92522;92523	chr2:178537109;178537108;178537107	chr2:179401836;179401835;179401834
N2B	24269	73030;73031;73032	chr2:178537109;178537108;178537107	chr2:179401836;179401835;179401834
Novex-1	24394	73405;73406;73407	chr2:178537109;178537108;178537107	chr2:179401836;179401835;179401834
Novex-2	24461	73606;73607;73608	chr2:178537109;178537108;178537107	chr2:179401836;179401835;179401834
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: Fn3-130
• Domain position: 45
• Structural Position: 54
• Q(SASA): 0.56
• 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	None	None	0.716	N	0.473	0.299	0.201204373187	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
K/R	rs1178919533	None	0.035	N	0.305	0.115	0.222439326576	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/R	rs1178919533	None	0.035	N	0.305	0.115	0.222439326576	gnomAD-4.0.0	2.5638E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.78794E-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	0.4083	ambiguous	0.3781	ambiguous	-0.015	Destabilizing	0.87	D	0.499	neutral	None	None	None	None	N
K/C	0.8505	likely_pathogenic	0.8338	pathogenic	-0.33	Destabilizing	0.998	D	0.686	prob.neutral	None	None	None	None	N
K/D	0.6855	likely_pathogenic	0.6663	pathogenic	-0.121	Destabilizing	0.959	D	0.573	neutral	None	None	None	None	N
K/E	0.2118	likely_benign	0.1914	benign	-0.132	Destabilizing	0.716	D	0.473	neutral	N	0.468012696	None	None	N
K/F	0.9003	likely_pathogenic	0.8875	pathogenic	-0.309	Destabilizing	0.994	D	0.638	neutral	None	None	None	None	N
K/G	0.4941	ambiguous	0.4643	ambiguous	-0.175	Destabilizing	0.959	D	0.449	neutral	None	None	None	None	N
K/H	0.5428	ambiguous	0.4899	ambiguous	-0.401	Destabilizing	0.994	D	0.575	neutral	None	None	None	None	N
K/I	0.5008	ambiguous	0.4772	ambiguous	0.322	Stabilizing	0.979	D	0.644	neutral	None	None	None	None	N
K/L	0.5163	ambiguous	0.5072	ambiguous	0.322	Stabilizing	0.959	D	0.449	neutral	None	None	None	None	N
K/M	0.4036	ambiguous	0.3773	ambiguous	0.105	Stabilizing	0.998	D	0.585	neutral	N	0.473445926	None	None	N
K/N	0.5461	ambiguous	0.5245	ambiguous	0.101	Stabilizing	0.946	D	0.551	neutral	N	0.463238808	None	None	N
K/P	0.787	likely_pathogenic	0.8428	pathogenic	0.235	Stabilizing	0.979	D	0.559	neutral	None	None	None	None	N
K/Q	0.2016	likely_benign	0.1721	benign	-0.084	Destabilizing	0.946	D	0.543	neutral	N	0.511899546	None	None	N
K/R	0.1066	likely_benign	0.0963	benign	-0.108	Destabilizing	0.035	N	0.305	neutral	N	0.495468656	None	None	N
K/S	0.4967	ambiguous	0.4645	ambiguous	-0.334	Destabilizing	0.87	D	0.499	neutral	None	None	None	None	N
K/T	0.2447	likely_benign	0.2178	benign	-0.213	Destabilizing	0.946	D	0.533	neutral	N	0.489004044	None	None	N
K/V	0.4223	ambiguous	0.3787	ambiguous	0.235	Stabilizing	0.959	D	0.575	neutral	None	None	None	None	N
K/W	0.9056	likely_pathogenic	0.8933	pathogenic	-0.351	Destabilizing	0.998	D	0.706	prob.neutral	None	None	None	None	N
K/Y	0.841	likely_pathogenic	0.8238	pathogenic	0.004	Stabilizing	0.979	D	0.608	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.