TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17558	52897;52898;52899	chr2:178608211;178608210;178608209	chr2:179472938;179472937;179472936
N2AB	15917	47974;47975;47976	chr2:178608211;178608210;178608209	chr2:179472938;179472937;179472936
N2A	14990	45193;45194;45195	chr2:178608211;178608210;178608209	chr2:179472938;179472937;179472936
N2B	8493	25702;25703;25704	chr2:178608211;178608210;178608209	chr2:179472938;179472937;179472936
Novex-1	8618	26077;26078;26079	chr2:178608211;178608210;178608209	chr2:179472938;179472937;179472936
Novex-2	8685	26278;26279;26280	chr2:178608211;178608210;178608209	chr2:179472938;179472937;179472936
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: Fn3-15
• Domain position: 89
• Structural Position: 123
• Q(SASA): 0.5864
• 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	rs374845620	-0.809	1.0	N	0.851	0.327	None	gnomAD-2.1.1	4.16E-06	None	None	None	None	I	None	6.61E-05	0	None	0	0	None	0	None	0	0	0
P/S	rs374845620	-0.809	1.0	N	0.851	0.327	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	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	0.0982	likely_benign	0.0938	benign	-1.648	Destabilizing	0.999	D	0.861	deleterious	N	0.486539742	None	None	I
P/C	0.7542	likely_pathogenic	0.6885	pathogenic	-0.958	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	I
P/D	0.906	likely_pathogenic	0.8752	pathogenic	-1.306	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	I
P/E	0.6685	likely_pathogenic	0.632	pathogenic	-1.267	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	I
P/F	0.8552	likely_pathogenic	0.8103	pathogenic	-1.205	Destabilizing	1.0	D	0.91	deleterious	None	None	None	None	I
P/G	0.7629	likely_pathogenic	0.6949	pathogenic	-2.008	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	I
P/H	0.6979	likely_pathogenic	0.6399	pathogenic	-1.501	Destabilizing	1.0	D	0.894	deleterious	N	0.51265295	None	None	I
P/I	0.4662	ambiguous	0.4095	ambiguous	-0.738	Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	I
P/K	0.8387	likely_pathogenic	0.811	pathogenic	-1.188	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	I
P/L	0.3285	likely_benign	0.2881	benign	-0.738	Destabilizing	1.0	D	0.837	deleterious	N	0.468883115	None	None	I
P/M	0.5987	likely_pathogenic	0.5554	ambiguous	-0.528	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	I
P/N	0.8403	likely_pathogenic	0.7939	pathogenic	-1.017	Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	I
P/Q	0.5227	ambiguous	0.4729	ambiguous	-1.144	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	I
P/R	0.7174	likely_pathogenic	0.6659	pathogenic	-0.721	Destabilizing	1.0	D	0.912	deleterious	N	0.489015286	None	None	I
P/S	0.3434	ambiguous	0.2985	benign	-1.617	Destabilizing	1.0	D	0.851	deleterious	N	0.513552985	None	None	I
P/T	0.3092	likely_benign	0.2549	benign	-1.463	Destabilizing	1.0	D	0.849	deleterious	N	0.466262995	None	None	I
P/V	0.305	likely_benign	0.2668	benign	-1.007	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	I
P/W	0.9526	likely_pathogenic	0.9324	pathogenic	-1.427	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	I
P/Y	0.8671	likely_pathogenic	0.8269	pathogenic	-1.121	Destabilizing	1.0	D	0.913	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.