TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33416	100471;100472;100473	chr2:178536501;178536500;178536499	chr2:179401228;179401227;179401226
N2AB	31775	95548;95549;95550	chr2:178536501;178536500;178536499	chr2:179401228;179401227;179401226
N2A	30848	92767;92768;92769	chr2:178536501;178536500;178536499	chr2:179401228;179401227;179401226
N2B	24351	73276;73277;73278	chr2:178536501;178536500;178536499	chr2:179401228;179401227;179401226
Novex-1	24476	73651;73652;73653	chr2:178536501;178536500;178536499	chr2:179401228;179401227;179401226
Novex-2	24543	73852;73853;73854	chr2:178536501;178536500;178536499	chr2:179401228;179401227;179401226
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: Fn3-131
• Domain position: 25
• Structural Position: 27
• Q(SASA): 0.1761
• 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	0.849	0.634	0.576080139486	gnomAD-4.0.0	1.73458E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.70103E-05	0
P/T	rs1691567099	None	1.0	D	0.846	0.686	0.627645487632	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	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	0.5749	likely_pathogenic	0.6064	pathogenic	-1.591	Destabilizing	1.0	D	0.831	deleterious	D	0.584847332	None	None	N
P/C	0.9676	likely_pathogenic	0.9712	pathogenic	-1.097	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
P/D	0.9957	likely_pathogenic	0.997	pathogenic	-1.437	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
P/E	0.9878	likely_pathogenic	0.9915	pathogenic	-1.447	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
P/F	0.9967	likely_pathogenic	0.9978	pathogenic	-1.362	Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
P/G	0.9587	likely_pathogenic	0.9675	pathogenic	-1.911	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
P/H	0.9817	likely_pathogenic	0.9881	pathogenic	-1.474	Destabilizing	1.0	D	0.88	deleterious	D	0.617723631	None	None	N
P/I	0.9727	likely_pathogenic	0.9786	pathogenic	-0.812	Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
P/K	0.9915	likely_pathogenic	0.9952	pathogenic	-1.339	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
P/L	0.9004	likely_pathogenic	0.9283	pathogenic	-0.812	Destabilizing	1.0	D	0.912	deleterious	D	0.61671461	None	None	N
P/M	0.9816	likely_pathogenic	0.9864	pathogenic	-0.582	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
P/N	0.9925	likely_pathogenic	0.9948	pathogenic	-1.086	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
P/Q	0.9715	likely_pathogenic	0.9821	pathogenic	-1.267	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
P/R	0.9748	likely_pathogenic	0.9846	pathogenic	-0.79	Destabilizing	1.0	D	0.897	deleterious	D	0.617521827	None	None	N
P/S	0.8862	likely_pathogenic	0.9139	pathogenic	-1.594	Destabilizing	1.0	D	0.849	deleterious	D	0.560066435	None	None	N
P/T	0.8602	likely_pathogenic	0.8987	pathogenic	-1.486	Destabilizing	1.0	D	0.846	deleterious	D	0.591781911	None	None	N
P/V	0.9138	likely_pathogenic	0.926	pathogenic	-1.037	Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
P/W	0.999	likely_pathogenic	0.9993	pathogenic	-1.527	Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
P/Y	0.9968	likely_pathogenic	0.998	pathogenic	-1.252	Destabilizing	1.0	D	0.91	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.