TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17571	52936;52937;52938	chr2:178608076;178608075;178608074	chr2:179472803;179472802;179472801
N2AB	15930	48013;48014;48015	chr2:178608076;178608075;178608074	chr2:179472803;179472802;179472801
N2A	15003	45232;45233;45234	chr2:178608076;178608075;178608074	chr2:179472803;179472802;179472801
N2B	8506	25741;25742;25743	chr2:178608076;178608075;178608074	chr2:179472803;179472802;179472801
Novex-1	8631	26116;26117;26118	chr2:178608076;178608075;178608074	chr2:179472803;179472802;179472801
Novex-2	8698	26317;26318;26319	chr2:178608076;178608075;178608074	chr2:179472803;179472802;179472801
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-16
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.1313
• 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
P/S	None	None	1.0	D	0.795	0.568	0.766478737258	gnomAD-4.0.0	1.59568E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.03527E-05

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	0.7631	likely_pathogenic	0.7505	pathogenic	-2.102	Highly Destabilizing	1.0	D	0.745	deleterious	D	0.61250703	None	None	N
P/C	0.9796	likely_pathogenic	0.9807	pathogenic	-2.279	Highly Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
P/D	0.9984	likely_pathogenic	0.9987	pathogenic	-3.503	Highly Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
P/E	0.9961	likely_pathogenic	0.9966	pathogenic	-3.357	Highly Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
P/F	0.9993	likely_pathogenic	0.9992	pathogenic	-1.077	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
P/G	0.9883	likely_pathogenic	0.9891	pathogenic	-2.473	Highly Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
P/H	0.9961	likely_pathogenic	0.9961	pathogenic	-1.87	Destabilizing	1.0	D	0.791	deleterious	D	0.62893	None	None	N
P/I	0.9893	likely_pathogenic	0.9888	pathogenic	-1.083	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
P/K	0.9975	likely_pathogenic	0.9975	pathogenic	-1.824	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
P/L	0.9622	likely_pathogenic	0.9591	pathogenic	-1.083	Destabilizing	1.0	D	0.815	deleterious	D	0.612305226	None	None	N
P/M	0.9944	likely_pathogenic	0.9938	pathogenic	-1.497	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
P/N	0.9987	likely_pathogenic	0.9988	pathogenic	-2.232	Highly Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
P/Q	0.9935	likely_pathogenic	0.9938	pathogenic	-2.198	Highly Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
P/R	0.9899	likely_pathogenic	0.9903	pathogenic	-1.508	Destabilizing	1.0	D	0.823	deleterious	D	0.62893	None	None	N
P/S	0.9718	likely_pathogenic	0.9726	pathogenic	-2.592	Highly Destabilizing	1.0	D	0.795	deleterious	D	0.612708835	None	None	N
P/T	0.9691	likely_pathogenic	0.9698	pathogenic	-2.344	Highly Destabilizing	1.0	D	0.805	deleterious	D	0.62893	None	None	N
P/V	0.9595	likely_pathogenic	0.9575	pathogenic	-1.402	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
P/W	0.9996	likely_pathogenic	0.9996	pathogenic	-1.469	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
P/Y	0.9992	likely_pathogenic	0.9992	pathogenic	-1.258	Destabilizing	1.0	D	0.807	deleterious	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.