TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16156	48691;48692;48693	chr2:178615479;178615478;178615477	chr2:179480206;179480205;179480204
N2AB	14515	43768;43769;43770	chr2:178615479;178615478;178615477	chr2:179480206;179480205;179480204
N2A	13588	40987;40988;40989	chr2:178615479;178615478;178615477	chr2:179480206;179480205;179480204
N2B	7091	21496;21497;21498	chr2:178615479;178615478;178615477	chr2:179480206;179480205;179480204
Novex-1	7216	21871;21872;21873	chr2:178615479;178615478;178615477	chr2:179480206;179480205;179480204
Novex-2	7283	22072;22073;22074	chr2:178615479;178615478;178615477	chr2:179480206;179480205;179480204
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: Fn3-5
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.1003
• 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/S	rs373195648	-2.264	0.911	D	0.421	0.467	None	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
P/S	rs373195648	-2.264	0.911	D	0.421	0.467	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
P/S	rs373195648	-2.264	0.911	D	0.421	0.467	None	gnomAD-4.0.0	1.86202E-05	None	None	None	None	N	None	1.33811E-05	0	None	0	0	None	0	0	2.46131E-05	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	0.9233	likely_pathogenic	0.9102	pathogenic	-1.408	Destabilizing	0.983	D	0.658	prob.neutral	D	0.719844392	None	None	N
P/C	0.9919	likely_pathogenic	0.99	pathogenic	-2.066	Highly Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
P/D	0.9997	likely_pathogenic	0.9993	pathogenic	-3.472	Highly Destabilizing	0.998	D	0.769	deleterious	None	None	None	None	N
P/E	0.9989	likely_pathogenic	0.9979	pathogenic	-3.393	Highly Destabilizing	0.998	D	0.771	deleterious	None	None	None	None	N
P/F	0.9997	likely_pathogenic	0.9995	pathogenic	-0.924	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
P/G	0.9945	likely_pathogenic	0.9919	pathogenic	-1.729	Destabilizing	0.993	D	0.731	deleterious	None	None	None	None	N
P/H	0.9988	likely_pathogenic	0.998	pathogenic	-1.215	Destabilizing	1.0	D	0.753	deleterious	D	0.778180256	None	None	N
P/I	0.9958	likely_pathogenic	0.9941	pathogenic	-0.572	Destabilizing	0.999	D	0.8	deleterious	None	None	None	None	N
P/K	0.9992	likely_pathogenic	0.9986	pathogenic	-1.504	Destabilizing	0.998	D	0.755	deleterious	None	None	None	None	N
P/L	0.9816	likely_pathogenic	0.973	pathogenic	-0.572	Destabilizing	0.999	D	0.775	deleterious	D	0.689625286	None	None	N
P/M	0.9971	likely_pathogenic	0.996	pathogenic	-0.917	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
P/N	0.9995	likely_pathogenic	0.9992	pathogenic	-1.941	Destabilizing	0.998	D	0.789	deleterious	None	None	None	None	N
P/Q	0.998	likely_pathogenic	0.9967	pathogenic	-2.047	Highly Destabilizing	0.999	D	0.836	deleterious	None	None	None	None	N
P/R	0.9966	likely_pathogenic	0.9941	pathogenic	-1.103	Destabilizing	0.999	D	0.797	deleterious	D	0.776605312	None	None	N
P/S	0.9932	likely_pathogenic	0.9903	pathogenic	-2.194	Highly Destabilizing	0.911	D	0.421	neutral	D	0.705220096	None	None	N
P/T	0.9902	likely_pathogenic	0.9867	pathogenic	-2.015	Highly Destabilizing	0.995	D	0.787	deleterious	D	0.741221398	None	None	N
P/V	0.9866	likely_pathogenic	0.9824	pathogenic	-0.825	Destabilizing	0.999	D	0.766	deleterious	None	None	None	None	N
P/W	0.9998	likely_pathogenic	0.9997	pathogenic	-1.333	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
P/Y	0.9997	likely_pathogenic	0.9996	pathogenic	-0.991	Destabilizing	1.0	D	0.809	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.