TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21165	63718;63719;63720	chr2:178587914;178587913;178587912	chr2:179452641;179452640;179452639
N2AB	19524	58795;58796;58797	chr2:178587914;178587913;178587912	chr2:179452641;179452640;179452639
N2A	18597	56014;56015;56016	chr2:178587914;178587913;178587912	chr2:179452641;179452640;179452639
N2B	12100	36523;36524;36525	chr2:178587914;178587913;178587912	chr2:179452641;179452640;179452639
Novex-1	12225	36898;36899;36900	chr2:178587914;178587913;178587912	chr2:179452641;179452640;179452639
Novex-2	12292	37099;37100;37101	chr2:178587914;178587913;178587912	chr2:179452641;179452640;179452639
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: Fn3-41
• Domain position: 102
• Structural Position: 130
• Q(SASA): 0.0731
• 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/L	None	None	1.0	N	0.83	0.394	0.415564226483	gnomAD-4.0.0	2.77185E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.63498E-06	0	0
P/R	None	None	1.0	N	0.839	0.402	0.337868961071	gnomAD-4.0.0	6.92963E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.08746E-07	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	0.2386	likely_benign	0.2418	benign	-2.477	Highly Destabilizing	0.999	D	0.819	deleterious	N	0.413764419	None	None	N
P/C	0.8649	likely_pathogenic	0.8676	pathogenic	-2.371	Highly Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
P/D	0.9949	likely_pathogenic	0.9955	pathogenic	-3.46	Highly Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
P/E	0.9779	likely_pathogenic	0.9797	pathogenic	-3.218	Highly Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
P/F	0.9931	likely_pathogenic	0.9935	pathogenic	-1.26	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
P/G	0.8643	likely_pathogenic	0.8701	pathogenic	-2.976	Highly Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
P/H	0.9818	likely_pathogenic	0.9827	pathogenic	-2.561	Highly Destabilizing	1.0	D	0.816	deleterious	N	0.46640331	None	None	N
P/I	0.8151	likely_pathogenic	0.8141	pathogenic	-1.047	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
P/K	0.9861	likely_pathogenic	0.9864	pathogenic	-1.965	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
P/L	0.6493	likely_pathogenic	0.6531	pathogenic	-1.047	Destabilizing	1.0	D	0.83	deleterious	N	0.487624672	None	None	N
P/M	0.8737	likely_pathogenic	0.8716	pathogenic	-1.489	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
P/N	0.9761	likely_pathogenic	0.9769	pathogenic	-2.49	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
P/Q	0.9455	likely_pathogenic	0.9467	pathogenic	-2.266	Highly Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
P/R	0.961	likely_pathogenic	0.9608	pathogenic	-1.837	Destabilizing	1.0	D	0.839	deleterious	N	0.465389352	None	None	N
P/S	0.7638	likely_pathogenic	0.7682	pathogenic	-2.992	Highly Destabilizing	1.0	D	0.761	deleterious	N	0.465135862	None	None	N
P/T	0.5616	ambiguous	0.5567	ambiguous	-2.62	Highly Destabilizing	1.0	D	0.771	deleterious	N	0.485664589	None	None	N
P/V	0.5683	likely_pathogenic	0.5649	pathogenic	-1.504	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
P/W	0.9975	likely_pathogenic	0.9977	pathogenic	-1.751	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
P/Y	0.993	likely_pathogenic	0.9935	pathogenic	-1.539	Destabilizing	1.0	D	0.864	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.