TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6111	18556;18557;18558	chr2:178729922;178729921;178729920	chr2:179594649;179594648;179594647
N2AB	5794	17605;17606;17607	chr2:178729922;178729921;178729920	chr2:179594649;179594648;179594647
N2A	4867	14824;14825;14826	chr2:178729922;178729921;178729920	chr2:179594649;179594648;179594647
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Ig-45
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.2302
• 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	rs753241275	-1.411	1.0	N	0.821	0.513	0.507213507908	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	2.93E-05	None	0	0	None	0	None	0	0	0
P/H	rs753241275	-1.411	1.0	N	0.821	0.513	0.507213507908	gnomAD-4.0.0	1.59376E-06	None	None	None	None	N	None	0	2.29442E-05	None	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	0.2257	likely_benign	0.2071	benign	-1.596	Destabilizing	1.0	D	0.772	deleterious	N	0.494512696	None	None	N
P/C	0.8718	likely_pathogenic	0.8411	pathogenic	-0.982	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
P/D	0.9246	likely_pathogenic	0.8886	pathogenic	-1.628	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
P/E	0.8092	likely_pathogenic	0.7605	pathogenic	-1.528	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
P/F	0.8291	likely_pathogenic	0.7977	pathogenic	-1.008	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
P/G	0.7503	likely_pathogenic	0.7102	pathogenic	-2.015	Highly Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
P/H	0.7394	likely_pathogenic	0.6743	pathogenic	-1.702	Destabilizing	1.0	D	0.821	deleterious	N	0.504173934	None	None	N
P/I	0.4871	ambiguous	0.4768	ambiguous	-0.496	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
P/K	0.8656	likely_pathogenic	0.8156	pathogenic	-1.398	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
P/L	0.2016	likely_benign	0.2313	benign	-0.496	Destabilizing	1.0	D	0.859	deleterious	N	0.408020243	None	None	N
P/M	0.557	ambiguous	0.5482	ambiguous	-0.395	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
P/N	0.8565	likely_pathogenic	0.8118	pathogenic	-1.328	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
P/Q	0.6413	likely_pathogenic	0.5861	pathogenic	-1.337	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
P/R	0.7378	likely_pathogenic	0.6837	pathogenic	-1.081	Destabilizing	1.0	D	0.863	deleterious	N	0.52177121	None	None	N
P/S	0.5861	likely_pathogenic	0.5166	ambiguous	-1.879	Destabilizing	1.0	D	0.819	deleterious	N	0.503413466	None	None	N
P/T	0.3693	ambiguous	0.3232	benign	-1.653	Destabilizing	1.0	D	0.825	deleterious	N	0.510161415	None	None	N
P/V	0.3556	ambiguous	0.3448	ambiguous	-0.83	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
P/W	0.948	likely_pathogenic	0.9333	pathogenic	-1.367	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
P/Y	0.8694	likely_pathogenic	0.8192	pathogenic	-1.01	Destabilizing	1.0	D	0.843	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.