TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28059	84400;84401;84402	chr2:178561957;178561956;178561955	chr2:179426684;179426683;179426682
N2AB	26418	79477;79478;79479	chr2:178561957;178561956;178561955	chr2:179426684;179426683;179426682
N2A	25491	76696;76697;76698	chr2:178561957;178561956;178561955	chr2:179426684;179426683;179426682
N2B	18994	57205;57206;57207	chr2:178561957;178561956;178561955	chr2:179426684;179426683;179426682
Novex-1	19119	57580;57581;57582	chr2:178561957;178561956;178561955	chr2:179426684;179426683;179426682
Novex-2	19186	57781;57782;57783	chr2:178561957;178561956;178561955	chr2:179426684;179426683;179426682
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-92
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.1285
• 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/A	rs1228328567	-2.448	0.919	D	0.807	0.712	0.597483089494	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
P/A	rs1228328567	-2.448	0.919	D	0.807	0.712	0.597483089494	gnomAD-4.0.0	3.1859E-06	None	None	None	None	N	None	5.66123E-05	0	None	0	0	None	0	0	2.86164E-06	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	0.2985	likely_benign	0.1928	benign	-2.092	Highly Destabilizing	0.919	D	0.807	deleterious	D	0.560759339	None	None	N
P/C	0.8045	likely_pathogenic	0.7059	pathogenic	-2.09	Highly Destabilizing	1.0	D	0.929	deleterious	None	None	None	None	N
P/D	0.9876	likely_pathogenic	0.9757	pathogenic	-3.276	Highly Destabilizing	0.998	D	0.86	deleterious	None	None	None	None	N
P/E	0.952	likely_pathogenic	0.9159	pathogenic	-3.03	Highly Destabilizing	0.995	D	0.868	deleterious	None	None	None	None	N
P/F	0.9873	likely_pathogenic	0.9715	pathogenic	-0.966	Destabilizing	0.998	D	0.949	deleterious	None	None	None	None	N
P/G	0.9282	likely_pathogenic	0.8655	pathogenic	-2.603	Highly Destabilizing	0.995	D	0.891	deleterious	None	None	None	None	N
P/H	0.9589	likely_pathogenic	0.9179	pathogenic	-2.375	Highly Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	N
P/I	0.6777	likely_pathogenic	0.5262	ambiguous	-0.635	Destabilizing	0.982	D	0.906	deleterious	None	None	None	None	N
P/K	0.9635	likely_pathogenic	0.936	pathogenic	-1.622	Destabilizing	0.995	D	0.87	deleterious	None	None	None	None	N
P/L	0.69	likely_pathogenic	0.5413	ambiguous	-0.635	Destabilizing	0.976	D	0.882	deleterious	D	0.598339653	None	None	N
P/M	0.8831	likely_pathogenic	0.778	pathogenic	-1.187	Destabilizing	0.999	D	0.923	deleterious	None	None	None	None	N
P/N	0.9784	likely_pathogenic	0.9536	pathogenic	-2.157	Highly Destabilizing	0.998	D	0.907	deleterious	None	None	None	None	N
P/Q	0.9128	likely_pathogenic	0.8474	pathogenic	-1.917	Destabilizing	0.998	D	0.866	deleterious	D	0.538673337	None	None	N
P/R	0.9265	likely_pathogenic	0.8788	pathogenic	-1.607	Destabilizing	0.994	D	0.917	deleterious	D	0.560930783	None	None	N
P/S	0.7746	likely_pathogenic	0.6244	pathogenic	-2.624	Highly Destabilizing	0.994	D	0.86	deleterious	D	0.582088127	None	None	N
P/T	0.441	ambiguous	0.2895	benign	-2.245	Highly Destabilizing	0.988	D	0.83	deleterious	D	0.570433447	None	None	N
P/V	0.417	ambiguous	0.2931	benign	-1.1	Destabilizing	0.18	N	0.749	deleterious	None	None	None	None	N
P/W	0.9967	likely_pathogenic	0.9926	pathogenic	-1.538	Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
P/Y	0.9912	likely_pathogenic	0.9802	pathogenic	-1.241	Destabilizing	0.999	D	0.949	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.