TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6500	19723;19724;19725	chr2:178728326;178728325;178728324	chr2:179593053;179593052;179593051
N2AB	6183	18772;18773;18774	chr2:178728326;178728325;178728324	chr2:179593053;179593052;179593051
N2A	5256	15991;15992;15993	chr2:178728326;178728325;178728324	chr2:179593053;179593052;179593051
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: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Ig-49
• Domain position: 20
• Structural Position: 30
• Q(SASA): 0.0886
• 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
M/V	None	None	0.007	N	0.389	0.32	0.42538462244	gnomAD-4.0.0	1.59478E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86192E-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
M/A	0.8167	likely_pathogenic	0.8882	pathogenic	-2.369	Highly Destabilizing	0.228	N	0.565	neutral	None	None	None	None	N
M/C	0.9461	likely_pathogenic	0.9658	pathogenic	-2.147	Highly Destabilizing	0.94	D	0.753	deleterious	None	None	None	None	N
M/D	0.996	likely_pathogenic	0.9979	pathogenic	-2.193	Highly Destabilizing	0.94	D	0.802	deleterious	None	None	None	None	N
M/E	0.9659	likely_pathogenic	0.9808	pathogenic	-1.969	Destabilizing	0.816	D	0.731	prob.delet.	None	None	None	None	N
M/F	0.364	ambiguous	0.3893	ambiguous	-1.106	Destabilizing	0.418	N	0.571	neutral	None	None	None	None	N
M/G	0.9489	likely_pathogenic	0.9701	pathogenic	-2.799	Highly Destabilizing	0.593	D	0.739	prob.delet.	None	None	None	None	N
M/H	0.9579	likely_pathogenic	0.9761	pathogenic	-2.312	Highly Destabilizing	0.983	D	0.839	deleterious	None	None	None	None	N
M/I	0.5334	ambiguous	0.643	pathogenic	-1.112	Destabilizing	None	N	0.249	neutral	N	0.453769254	None	None	N
M/K	0.8346	likely_pathogenic	0.8878	pathogenic	-1.351	Destabilizing	0.523	D	0.611	neutral	N	0.505647144	None	None	N
M/L	0.1228	likely_benign	0.1533	benign	-1.112	Destabilizing	None	N	0.236	neutral	N	0.340664674	None	None	N
M/N	0.9779	likely_pathogenic	0.988	pathogenic	-1.739	Destabilizing	0.94	D	0.779	deleterious	None	None	None	None	N
M/P	0.9918	likely_pathogenic	0.9953	pathogenic	-1.519	Destabilizing	0.94	D	0.779	deleterious	None	None	None	None	N
M/Q	0.8588	likely_pathogenic	0.9056	pathogenic	-1.485	Destabilizing	0.94	D	0.63	neutral	None	None	None	None	N
M/R	0.8275	likely_pathogenic	0.8903	pathogenic	-1.431	Destabilizing	0.921	D	0.697	prob.neutral	N	0.505647144	None	None	N
M/S	0.9329	likely_pathogenic	0.9633	pathogenic	-2.223	Highly Destabilizing	0.593	D	0.613	neutral	None	None	None	None	N
M/T	0.7452	likely_pathogenic	0.851	pathogenic	-1.881	Destabilizing	0.183	N	0.601	neutral	N	0.494037349	None	None	N
M/V	0.1761	likely_benign	0.223	benign	-1.519	Destabilizing	0.007	N	0.389	neutral	N	0.484900238	None	None	N
M/W	0.8353	likely_pathogenic	0.8813	pathogenic	-1.341	Destabilizing	0.983	D	0.746	deleterious	None	None	None	None	N
M/Y	0.86	likely_pathogenic	0.8937	pathogenic	-1.338	Destabilizing	0.836	D	0.707	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.