TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22156	66691;66692;66693	chr2:178581802;178581801;178581800	chr2:179446529;179446528;179446527
N2AB	20515	61768;61769;61770	chr2:178581802;178581801;178581800	chr2:179446529;179446528;179446527
N2A	19588	58987;58988;58989	chr2:178581802;178581801;178581800	chr2:179446529;179446528;179446527
N2B	13091	39496;39497;39498	chr2:178581802;178581801;178581800	chr2:179446529;179446528;179446527
Novex-1	13216	39871;39872;39873	chr2:178581802;178581801;178581800	chr2:179446529;179446528;179446527
Novex-2	13283	40072;40073;40074	chr2:178581802;178581801;178581800	chr2:179446529;179446528;179446527
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: Fn3-49
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.5247
• 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/S	None	None	1.0	N	0.849	0.327	0.384086055536	gnomAD-4.0.0	6.93322E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.2012E-05	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	0.1846	likely_benign	0.196	benign	-0.682	Destabilizing	0.999	D	0.825	deleterious	N	0.473221073	None	None	I
P/C	0.7146	likely_pathogenic	0.7314	pathogenic	-0.72	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	I
P/D	0.9462	likely_pathogenic	0.956	pathogenic	-0.114	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	I
P/E	0.6838	likely_pathogenic	0.6871	pathogenic	-0.219	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	I
P/F	0.8528	likely_pathogenic	0.8629	pathogenic	-0.848	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	I
P/G	0.8268	likely_pathogenic	0.8494	pathogenic	-0.829	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	I
P/H	0.5691	likely_pathogenic	0.6027	pathogenic	-0.324	Destabilizing	1.0	D	0.864	deleterious	N	0.508814608	None	None	I
P/I	0.3713	ambiguous	0.397	ambiguous	-0.44	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	I
P/K	0.4506	ambiguous	0.4573	ambiguous	-0.396	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	I
P/L	0.2164	likely_benign	0.2394	benign	-0.44	Destabilizing	1.0	D	0.83	deleterious	N	0.467539988	None	None	I
P/M	0.5377	ambiguous	0.5545	ambiguous	-0.362	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	I
P/N	0.8584	likely_pathogenic	0.8772	pathogenic	-0.158	Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	I
P/Q	0.3725	ambiguous	0.3868	ambiguous	-0.419	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
P/R	0.3097	likely_benign	0.3373	benign	0.119	Stabilizing	1.0	D	0.858	deleterious	N	0.4780866	None	None	I
P/S	0.4796	ambiguous	0.5143	ambiguous	-0.622	Destabilizing	1.0	D	0.849	deleterious	N	0.479567857	None	None	I
P/T	0.279	likely_benign	0.3103	benign	-0.622	Destabilizing	1.0	D	0.837	deleterious	N	0.507293671	None	None	I
P/V	0.2593	likely_benign	0.2885	benign	-0.485	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	I
P/W	0.9457	likely_pathogenic	0.9541	pathogenic	-0.876	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	I
P/Y	0.846	likely_pathogenic	0.8651	pathogenic	-0.579	Destabilizing	1.0	D	0.869	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.