TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21117	63574;63575;63576	chr2:178588058;178588057;178588056	chr2:179452785;179452784;179452783
N2AB	19476	58651;58652;58653	chr2:178588058;178588057;178588056	chr2:179452785;179452784;179452783
N2A	18549	55870;55871;55872	chr2:178588058;178588057;178588056	chr2:179452785;179452784;179452783
N2B	12052	36379;36380;36381	chr2:178588058;178588057;178588056	chr2:179452785;179452784;179452783
Novex-1	12177	36754;36755;36756	chr2:178588058;178588057;178588056	chr2:179452785;179452784;179452783
Novex-2	12244	36955;36956;36957	chr2:178588058;178588057;178588056	chr2:179452785;179452784;179452783
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: Fn3-41
• Domain position: 54
• Structural Position: 66
• Q(SASA): 0.6775
• 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	rs1400590737	0.43	0.999	N	0.623	0.398	0.380901646489	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
K/E	rs1400590737	0.43	0.999	N	0.623	0.398	0.380901646489	gnomAD-4.0.0	1.59297E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43353E-05	0
K/Q	None	None	1.0	N	0.674	0.378	0.223847106136	gnomAD-4.0.0	1.59297E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86128E-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	0.4833	ambiguous	0.5027	ambiguous	-0.123	Destabilizing	0.999	D	0.651	neutral	None	None	None	None	N
K/C	0.6802	likely_pathogenic	0.6852	pathogenic	-0.133	Destabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
K/D	0.7359	likely_pathogenic	0.7504	pathogenic	-0.012	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	N
K/E	0.2034	likely_benign	0.2069	benign	0.047	Stabilizing	0.999	D	0.623	neutral	N	0.48731332	None	None	N
K/F	0.723	likely_pathogenic	0.7454	pathogenic	0.009	Stabilizing	1.0	D	0.671	neutral	None	None	None	None	N
K/G	0.6119	likely_pathogenic	0.6362	pathogenic	-0.413	Destabilizing	1.0	D	0.638	neutral	None	None	None	None	N
K/H	0.3034	likely_benign	0.2996	benign	-0.69	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	N
K/I	0.2772	likely_benign	0.2928	benign	0.59	Stabilizing	1.0	D	0.687	prob.neutral	N	0.444946622	None	None	N
K/L	0.3325	likely_benign	0.345	ambiguous	0.59	Stabilizing	1.0	D	0.638	neutral	None	None	None	None	N
K/M	0.2274	likely_benign	0.2401	benign	0.269	Stabilizing	1.0	D	0.657	neutral	None	None	None	None	N
K/N	0.5195	ambiguous	0.5376	ambiguous	0.06	Stabilizing	1.0	D	0.701	prob.neutral	N	0.516190645	None	None	N
K/P	0.939	likely_pathogenic	0.9435	pathogenic	0.382	Stabilizing	1.0	D	0.664	neutral	None	None	None	None	N
K/Q	0.1184	likely_benign	0.1165	benign	-0.02	Destabilizing	1.0	D	0.674	neutral	N	0.463222952	None	None	N
K/R	0.0898	likely_benign	0.0879	benign	-0.273	Destabilizing	0.999	D	0.578	neutral	N	0.459684001	None	None	N
K/S	0.532	ambiguous	0.5465	ambiguous	-0.416	Destabilizing	0.999	D	0.668	neutral	None	None	None	None	N
K/T	0.2105	likely_benign	0.2228	benign	-0.186	Destabilizing	1.0	D	0.656	neutral	N	0.442714394	None	None	N
K/V	0.2673	likely_benign	0.28	benign	0.382	Stabilizing	1.0	D	0.661	neutral	None	None	None	None	N
K/W	0.7289	likely_pathogenic	0.74	pathogenic	0.013	Stabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
K/Y	0.6187	likely_pathogenic	0.6301	pathogenic	0.307	Stabilizing	1.0	D	0.667	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.