TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1463	4612;4613;4614	chr2:178777797;178777796;178777795	chr2:179642524;179642523;179642522
N2AB	1463	4612;4613;4614	chr2:178777797;178777796;178777795	chr2:179642524;179642523;179642522
N2A	1463	4612;4613;4614	chr2:178777797;178777796;178777795	chr2:179642524;179642523;179642522
N2B	1417	4474;4475;4476	chr2:178777797;178777796;178777795	chr2:179642524;179642523;179642522
Novex-1	1417	4474;4475;4476	chr2:178777797;178777796;178777795	chr2:179642524;179642523;179642522
Novex-2	1417	4474;4475;4476	chr2:178777797;178777796;178777795	chr2:179642524;179642523;179642522
Novex-3	1463	4612;4613;4614	chr2:178777797;178777796;178777795	chr2:179642524;179642523;179642522

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-6
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.2015
• Predicted PPI site: I

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
P/A	rs2092386861	None	1.0	D	0.738	0.675	0.640003636113	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-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
P/A	0.5808	likely_pathogenic	0.5364	ambiguous	-1.517	Destabilizing	1.0	D	0.738	prob.delet.	D	0.642823462	None	None	I
P/C	0.9899	likely_pathogenic	0.989	pathogenic	-0.972	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	I
P/D	0.9966	likely_pathogenic	0.9953	pathogenic	-1.866	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	I
P/E	0.9935	likely_pathogenic	0.9899	pathogenic	-1.637	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	I
P/F	0.9985	likely_pathogenic	0.9979	pathogenic	-0.835	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	I
P/G	0.943	likely_pathogenic	0.9357	pathogenic	-2.021	Highly Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	I
P/H	0.996	likely_pathogenic	0.994	pathogenic	-1.65	Destabilizing	1.0	D	0.793	deleterious	D	0.740556774	None	None	I
P/I	0.982	likely_pathogenic	0.9744	pathogenic	-0.123	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	I
P/K	0.9975	likely_pathogenic	0.996	pathogenic	-1.243	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	I
P/L	0.8985	likely_pathogenic	0.8664	pathogenic	-0.123	Destabilizing	1.0	D	0.828	deleterious	D	0.526011862	None	None	I
P/M	0.9851	likely_pathogenic	0.9794	pathogenic	-0.195	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	I
P/N	0.9944	likely_pathogenic	0.9923	pathogenic	-1.638	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	I
P/Q	0.9909	likely_pathogenic	0.9863	pathogenic	-1.428	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	I
P/R	0.9942	likely_pathogenic	0.991	pathogenic	-1.226	Destabilizing	1.0	D	0.833	deleterious	D	0.798718311	None	None	I
P/S	0.9493	likely_pathogenic	0.9332	pathogenic	-2.223	Highly Destabilizing	1.0	D	0.815	deleterious	D	0.676659687	None	None	I
P/T	0.9216	likely_pathogenic	0.8894	pathogenic	-1.839	Destabilizing	1.0	D	0.824	deleterious	D	0.640537559	None	None	I
P/V	0.9444	likely_pathogenic	0.926	pathogenic	-0.561	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
P/W	0.9998	likely_pathogenic	0.9996	pathogenic	-1.279	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	I
P/Y	0.9992	likely_pathogenic	0.9987	pathogenic	-0.83	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	I

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.