TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29399	88420;88421;88422	chr2:178556959;178556958;178556957	chr2:179421686;179421685;179421684
N2AB	27758	83497;83498;83499	chr2:178556959;178556958;178556957	chr2:179421686;179421685;179421684
N2A	26831	80716;80717;80718	chr2:178556959;178556958;178556957	chr2:179421686;179421685;179421684
N2B	20334	61225;61226;61227	chr2:178556959;178556958;178556957	chr2:179421686;179421685;179421684
Novex-1	20459	61600;61601;61602	chr2:178556959;178556958;178556957	chr2:179421686;179421685;179421684
Novex-2	20526	61801;61802;61803	chr2:178556959;178556958;178556957	chr2:179421686;179421685;179421684
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Fn3-102
• Domain position: 65
• Structural Position: 96
• Q(SASA): 0.5488
• 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
G/A	rs1701744078	None	1.0	N	0.694	0.406	0.243972157842	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
G/A	rs1701744078	None	1.0	N	0.694	0.406	0.243972157842	gnomAD-4.0.0	2.56222E-06	None	None	None	None	I	None	3.38215E-05	0	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
G/A	0.3039	likely_benign	0.2215	benign	-0.174	Destabilizing	1.0	D	0.694	prob.neutral	N	0.489452451	None	None	I
G/C	0.4541	ambiguous	0.3568	ambiguous	-0.846	Destabilizing	1.0	D	0.747	deleterious	D	0.538031224	None	None	I
G/D	0.5018	ambiguous	0.3754	ambiguous	-0.145	Destabilizing	1.0	D	0.751	deleterious	N	0.492305347	None	None	I
G/E	0.6032	likely_pathogenic	0.4558	ambiguous	-0.303	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	I
G/F	0.901	likely_pathogenic	0.8267	pathogenic	-0.913	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	I
G/H	0.7135	likely_pathogenic	0.5856	pathogenic	-0.393	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	I
G/I	0.7864	likely_pathogenic	0.6853	pathogenic	-0.348	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	I
G/K	0.8551	likely_pathogenic	0.752	pathogenic	-0.522	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	I
G/L	0.8133	likely_pathogenic	0.7171	pathogenic	-0.348	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	I
G/M	0.8239	likely_pathogenic	0.7254	pathogenic	-0.443	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
G/N	0.433	ambiguous	0.3139	benign	-0.221	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	I
G/P	0.9647	likely_pathogenic	0.9435	pathogenic	-0.259	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
G/Q	0.673	likely_pathogenic	0.5378	ambiguous	-0.466	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	I
G/R	0.7287	likely_pathogenic	0.5883	pathogenic	-0.179	Destabilizing	1.0	D	0.781	deleterious	N	0.479070424	None	None	I
G/S	0.1616	likely_benign	0.1192	benign	-0.415	Destabilizing	1.0	D	0.758	deleterious	N	0.477562713	None	None	I
G/T	0.4123	ambiguous	0.2983	benign	-0.493	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	I
G/V	0.643	likely_pathogenic	0.5195	ambiguous	-0.259	Destabilizing	1.0	D	0.768	deleterious	D	0.526674919	None	None	I
G/W	0.8387	likely_pathogenic	0.7393	pathogenic	-1.054	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
G/Y	0.8206	likely_pathogenic	0.7105	pathogenic	-0.692	Destabilizing	1.0	D	0.757	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.