TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33037	99334;99335;99336	chr2:178538720;178538719;178538718	chr2:179403447;179403446;179403445
N2AB	31396	94411;94412;94413	chr2:178538720;178538719;178538718	chr2:179403447;179403446;179403445
N2A	30469	91630;91631;91632	chr2:178538720;178538719;178538718	chr2:179403447;179403446;179403445
N2B	23972	72139;72140;72141	chr2:178538720;178538719;178538718	chr2:179403447;179403446;179403445
Novex-1	24097	72514;72515;72516	chr2:178538720;178538719;178538718	chr2:179403447;179403446;179403445
Novex-2	24164	72715;72716;72717	chr2:178538720;178538719;178538718	chr2:179403447;179403446;179403445
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-129
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.3013
• 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
Y/C	rs1692914816	None	1.0	N	0.725	0.401	0.608945918356	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	2.88018E-04	0	None	0	0	0	0	0
Y/C	rs1692914816	None	1.0	N	0.725	0.401	0.608945918356	gnomAD-4.0.0	3.09847E-06	None	None	None	None	N	None	0	0	None	1.68908E-04	0	None	0	0	0	0	0
Y/H	None	None	0.999	N	0.682	0.399	0.532216101619	gnomAD-4.0.0	3.18263E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71687E-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
Y/A	0.8147	likely_pathogenic	0.8352	pathogenic	-2.053	Highly Destabilizing	0.992	D	0.667	neutral	None	None	None	None	N
Y/C	0.2061	likely_benign	0.2346	benign	-1.058	Destabilizing	1.0	D	0.725	prob.delet.	N	0.495802304	None	None	N
Y/D	0.9189	likely_pathogenic	0.9263	pathogenic	-2.696	Highly Destabilizing	0.999	D	0.756	deleterious	N	0.518210628	None	None	N
Y/E	0.9375	likely_pathogenic	0.9449	pathogenic	-2.468	Highly Destabilizing	0.999	D	0.726	prob.delet.	None	None	None	None	N
Y/F	0.1156	likely_benign	0.1199	benign	-0.592	Destabilizing	0.121	N	0.275	neutral	N	0.475928464	None	None	N
Y/G	0.7973	likely_pathogenic	0.8051	pathogenic	-2.468	Highly Destabilizing	0.999	D	0.732	prob.delet.	None	None	None	None	N
Y/H	0.3444	ambiguous	0.3807	ambiguous	-1.504	Destabilizing	0.999	D	0.682	prob.neutral	N	0.480102787	None	None	N
Y/I	0.674	likely_pathogenic	0.7269	pathogenic	-0.691	Destabilizing	0.995	D	0.647	neutral	None	None	None	None	N
Y/K	0.8591	likely_pathogenic	0.8639	pathogenic	-1.668	Destabilizing	0.999	D	0.721	prob.delet.	None	None	None	None	N
Y/L	0.6502	likely_pathogenic	0.6893	pathogenic	-0.691	Destabilizing	0.967	D	0.637	neutral	None	None	None	None	N
Y/M	0.7127	likely_pathogenic	0.7475	pathogenic	-0.538	Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	N
Y/N	0.588	likely_pathogenic	0.6241	pathogenic	-2.577	Highly Destabilizing	0.999	D	0.735	prob.delet.	N	0.518210628	None	None	N
Y/P	0.9977	likely_pathogenic	0.9982	pathogenic	-1.157	Destabilizing	0.999	D	0.758	deleterious	None	None	None	None	N
Y/Q	0.7767	likely_pathogenic	0.7987	pathogenic	-2.19	Highly Destabilizing	0.999	D	0.704	prob.neutral	None	None	None	None	N
Y/R	0.7655	likely_pathogenic	0.7582	pathogenic	-1.844	Destabilizing	0.999	D	0.739	prob.delet.	None	None	None	None	N
Y/S	0.5808	likely_pathogenic	0.6068	pathogenic	-2.852	Highly Destabilizing	0.999	D	0.716	prob.delet.	N	0.518641878	None	None	N
Y/T	0.7772	likely_pathogenic	0.805	pathogenic	-2.491	Highly Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	N
Y/V	0.5694	likely_pathogenic	0.6243	pathogenic	-1.157	Destabilizing	0.983	D	0.641	neutral	None	None	None	None	N
Y/W	0.5433	ambiguous	0.5875	pathogenic	-0.007	Destabilizing	1.0	D	0.688	prob.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.