TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8875	26848;26849;26850	chr2:178714035;178714034;178714033	chr2:179578762;179578761;179578760
N2AB	8558	25897;25898;25899	chr2:178714035;178714034;178714033	chr2:179578762;179578761;179578760
N2A	7631	23116;23117;23118	chr2:178714035;178714034;178714033	chr2:179578762;179578761;179578760
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-74
• Domain position: 46
• Structural Position: 115
• Q(SASA): 0.6034
• 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/I	rs1472784946	None	1.0	N	0.641	0.454	0.496036935653	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
K/I	rs1472784946	None	1.0	N	0.641	0.454	0.496036935653	gnomAD-4.0.0	1.31463E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.94048E-05	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	0.683	likely_pathogenic	0.7336	pathogenic	-0.735	Destabilizing	0.997	D	0.571	neutral	None	None	None	None	N
K/C	0.8376	likely_pathogenic	0.8581	pathogenic	-0.544	Destabilizing	1.0	D	0.643	neutral	None	None	None	None	N
K/D	0.8084	likely_pathogenic	0.8008	pathogenic	-0.225	Destabilizing	0.996	D	0.619	neutral	None	None	None	None	N
K/E	0.4916	ambiguous	0.5007	ambiguous	-0.07	Destabilizing	0.992	D	0.492	neutral	N	0.513256622	None	None	N
K/F	0.9072	likely_pathogenic	0.9224	pathogenic	-0.244	Destabilizing	1.0	D	0.61	neutral	None	None	None	None	N
K/G	0.7616	likely_pathogenic	0.8061	pathogenic	-1.147	Destabilizing	0.994	D	0.542	neutral	None	None	None	None	N
K/H	0.4231	ambiguous	0.4352	ambiguous	-1.442	Destabilizing	1.0	D	0.623	neutral	None	None	None	None	N
K/I	0.5713	likely_pathogenic	0.6135	pathogenic	0.36	Stabilizing	1.0	D	0.641	neutral	N	0.467924247	None	None	N
K/L	0.589	likely_pathogenic	0.6444	pathogenic	0.36	Stabilizing	0.999	D	0.572	neutral	None	None	None	None	N
K/M	0.4478	ambiguous	0.496	ambiguous	0.216	Stabilizing	1.0	D	0.617	neutral	None	None	None	None	N
K/N	0.6671	likely_pathogenic	0.6652	pathogenic	-0.651	Destabilizing	0.79	D	0.232	neutral	N	0.478258614	None	None	N
K/P	0.9403	likely_pathogenic	0.9422	pathogenic	0.024	Stabilizing	1.0	D	0.653	neutral	None	None	None	None	N
K/Q	0.2622	likely_benign	0.2842	benign	-0.591	Destabilizing	0.999	D	0.634	neutral	N	0.467924247	None	None	N
K/R	0.0855	likely_benign	0.091	benign	-0.743	Destabilizing	0.996	D	0.528	neutral	N	0.416953865	None	None	N
K/S	0.7171	likely_pathogenic	0.7457	pathogenic	-1.288	Destabilizing	0.994	D	0.514	neutral	None	None	None	None	N
K/T	0.3374	likely_benign	0.3801	ambiguous	-0.908	Destabilizing	0.998	D	0.637	neutral	N	0.486590096	None	None	N
K/V	0.5827	likely_pathogenic	0.6403	pathogenic	0.024	Stabilizing	1.0	D	0.614	neutral	None	None	None	None	N
K/W	0.8508	likely_pathogenic	0.8778	pathogenic	-0.158	Destabilizing	1.0	D	0.637	neutral	None	None	None	None	N
K/Y	0.7625	likely_pathogenic	0.7809	pathogenic	0.112	Stabilizing	1.0	D	0.607	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.