TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22644	68155;68156;68157	chr2:178579100;178579099;178579098	chr2:179443827;179443826;179443825
N2AB	21003	63232;63233;63234	chr2:178579100;178579099;178579098	chr2:179443827;179443826;179443825
N2A	20076	60451;60452;60453	chr2:178579100;178579099;178579098	chr2:179443827;179443826;179443825
N2B	13579	40960;40961;40962	chr2:178579100;178579099;178579098	chr2:179443827;179443826;179443825
Novex-1	13704	41335;41336;41337	chr2:178579100;178579099;178579098	chr2:179443827;179443826;179443825
Novex-2	13771	41536;41537;41538	chr2:178579100;178579099;178579098	chr2:179443827;179443826;179443825
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: Fn3-52
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.1363
• 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/R	rs1366675225	None	1.0	D	0.809	0.793	0.891885484271	gnomAD-4.0.0	1.59213E-06	None	None	None	None	N	None	0	0	None	0	2.78087E-05	None	0	0	0	0	0
P/S	None	None	1.0	D	0.737	0.788	0.744525733801	gnomAD-4.0.0	7.96079E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.4299E-05	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	0.9237	likely_pathogenic	0.9019	pathogenic	-1.488	Destabilizing	0.999	D	0.793	deleterious	D	0.611001525	None	None	N
P/C	0.9949	likely_pathogenic	0.9939	pathogenic	-1.956	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
P/D	0.9993	likely_pathogenic	0.9992	pathogenic	-3.3	Highly Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
P/E	0.9984	likely_pathogenic	0.998	pathogenic	-3.234	Highly Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
P/F	0.9997	likely_pathogenic	0.9996	pathogenic	-1.05	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
P/G	0.9946	likely_pathogenic	0.9941	pathogenic	-1.818	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
P/H	0.9983	likely_pathogenic	0.9977	pathogenic	-1.293	Destabilizing	1.0	D	0.771	deleterious	D	0.65316441	None	None	N
P/I	0.9959	likely_pathogenic	0.9937	pathogenic	-0.635	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
P/K	0.9988	likely_pathogenic	0.9985	pathogenic	-1.474	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
P/L	0.9826	likely_pathogenic	0.977	pathogenic	-0.635	Destabilizing	1.0	D	0.808	deleterious	D	0.636943245	None	None	N
P/M	0.9978	likely_pathogenic	0.9969	pathogenic	-0.891	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
P/N	0.9993	likely_pathogenic	0.9991	pathogenic	-1.812	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
P/Q	0.9981	likely_pathogenic	0.9973	pathogenic	-1.952	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
P/R	0.9953	likely_pathogenic	0.9945	pathogenic	-1.031	Destabilizing	1.0	D	0.809	deleterious	D	0.636943245	None	None	N
P/S	0.9941	likely_pathogenic	0.992	pathogenic	-2.12	Highly Destabilizing	1.0	D	0.737	deleterious	D	0.63674144	None	None	N
P/T	0.9892	likely_pathogenic	0.985	pathogenic	-1.952	Destabilizing	1.0	D	0.745	deleterious	D	0.652962606	None	None	N
P/V	0.9854	likely_pathogenic	0.9799	pathogenic	-0.892	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
P/W	0.9998	likely_pathogenic	0.9997	pathogenic	-1.423	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
P/Y	0.9995	likely_pathogenic	0.9993	pathogenic	-1.08	Destabilizing	1.0	D	0.823	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.