TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15883	47872;47873;47874	chr2:178617438;178617437;178617436	chr2:179482165;179482164;179482163
N2AB	14242	42949;42950;42951	chr2:178617438;178617437;178617436	chr2:179482165;179482164;179482163
N2A	13315	40168;40169;40170	chr2:178617438;178617437;178617436	chr2:179482165;179482164;179482163
N2B	6818	20677;20678;20679	chr2:178617438;178617437;178617436	chr2:179482165;179482164;179482163
Novex-1	6943	21052;21053;21054	chr2:178617438;178617437;178617436	chr2:179482165;179482164;179482163
Novex-2	7010	21253;21254;21255	chr2:178617438;178617437;178617436	chr2:179482165;179482164;179482163
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: Fn3-3
• Domain position: 25
• Structural Position: 27
• Q(SASA): 0.1027
• 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/H	None	None	1.0	D	0.882	0.624	0.591878746342	gnomAD-4.0.0	6.92158E-07	None	None	None	None	N	None	0	0	None	0	2.55245E-05	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	0.6499	likely_pathogenic	0.8036	pathogenic	-2.053	Highly Destabilizing	1.0	D	0.836	deleterious	D	0.627689573	None	None	N
P/C	0.9563	likely_pathogenic	0.9773	pathogenic	-1.439	Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
P/D	0.9971	likely_pathogenic	0.9973	pathogenic	-2.669	Highly Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
P/E	0.9945	likely_pathogenic	0.9953	pathogenic	-2.526	Highly Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
P/F	0.9979	likely_pathogenic	0.9987	pathogenic	-1.351	Destabilizing	1.0	D	0.908	deleterious	None	None	None	None	N
P/G	0.9614	likely_pathogenic	0.9777	pathogenic	-2.524	Highly Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
P/H	0.9882	likely_pathogenic	0.9907	pathogenic	-2.321	Highly Destabilizing	1.0	D	0.882	deleterious	D	0.770203239	None	None	N
P/I	0.9845	likely_pathogenic	0.9906	pathogenic	-0.773	Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
P/K	0.9972	likely_pathogenic	0.9969	pathogenic	-1.874	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
P/L	0.9351	likely_pathogenic	0.9562	pathogenic	-0.773	Destabilizing	1.0	D	0.914	deleterious	D	0.697762874	None	None	N
P/M	0.9894	likely_pathogenic	0.9941	pathogenic	-0.589	Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
P/N	0.9955	likely_pathogenic	0.9964	pathogenic	-1.975	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
P/Q	0.9881	likely_pathogenic	0.9909	pathogenic	-1.941	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
P/R	0.9873	likely_pathogenic	0.9876	pathogenic	-1.518	Destabilizing	1.0	D	0.899	deleterious	D	0.643569476	None	None	N
P/S	0.9154	likely_pathogenic	0.9528	pathogenic	-2.513	Highly Destabilizing	1.0	D	0.853	deleterious	D	0.545469534	None	None	N
P/T	0.9281	likely_pathogenic	0.955	pathogenic	-2.249	Highly Destabilizing	1.0	D	0.851	deleterious	D	0.687152389	None	None	N
P/V	0.9448	likely_pathogenic	0.9663	pathogenic	-1.171	Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
P/W	0.9993	likely_pathogenic	0.9995	pathogenic	-1.866	Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
P/Y	0.9981	likely_pathogenic	0.9987	pathogenic	-1.509	Destabilizing	1.0	D	0.913	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.