TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23520	70783;70784;70785	chr2:178575574;178575573;178575572	chr2:179440301;179440300;179440299
N2AB	21879	65860;65861;65862	chr2:178575574;178575573;178575572	chr2:179440301;179440300;179440299
N2A	20952	63079;63080;63081	chr2:178575574;178575573;178575572	chr2:179440301;179440300;179440299
N2B	14455	43588;43589;43590	chr2:178575574;178575573;178575572	chr2:179440301;179440300;179440299
Novex-1	14580	43963;43964;43965	chr2:178575574;178575573;178575572	chr2:179440301;179440300;179440299
Novex-2	14647	44164;44165;44166	chr2:178575574;178575573;178575572	chr2:179440301;179440300;179440299
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: Fn3-58
• Domain position: 86
• Structural Position: 120
• Q(SASA): 0.3512
• 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
P/L	rs763169614	-0.755	0.997	D	0.762	0.418	0.615473259424	gnomAD-2.1.1	1.21E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	2.67E-05	0
P/L	rs763169614	-0.755	0.997	D	0.762	0.418	0.615473259424	gnomAD-4.0.0	1.98434E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.60869E-05	0	0
P/R	rs763169614	-0.306	1.0	D	0.845	0.458	0.486779940545	gnomAD-2.1.1	3.19E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
P/R	rs763169614	-0.306	1.0	D	0.845	0.458	0.486779940545	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
P/R	rs763169614	-0.306	1.0	D	0.845	0.458	0.486779940545	gnomAD-4.0.0	6.57912E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.47089E-05	0	0
P/T	rs1296805014	-1.036	0.993	N	0.795	0.335	0.39843156188	gnomAD-2.1.1	3.19E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
P/T	rs1296805014	-1.036	0.993	N	0.795	0.335	0.39843156188	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
P/T	rs1296805014	-1.036	0.993	N	0.795	0.335	0.39843156188	gnomAD-4.0.0	6.57756E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.47076E-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	0.1202	likely_benign	0.1436	benign	-1.03	Destabilizing	0.932	D	0.645	neutral	N	0.472138799	None	None	I
P/C	0.6596	likely_pathogenic	0.741	pathogenic	-0.632	Destabilizing	0.999	D	0.85	deleterious	None	None	None	None	I
P/D	0.9166	likely_pathogenic	0.9543	pathogenic	-0.99	Destabilizing	0.99	D	0.807	deleterious	None	None	None	None	I
P/E	0.802	likely_pathogenic	0.8882	pathogenic	-1.087	Destabilizing	0.993	D	0.8	deleterious	None	None	None	None	I
P/F	0.683	likely_pathogenic	0.8063	pathogenic	-1.072	Destabilizing	0.789	D	0.651	neutral	None	None	None	None	I
P/G	0.4903	ambiguous	0.5301	ambiguous	-1.226	Destabilizing	0.997	D	0.721	prob.delet.	None	None	None	None	I
P/H	0.6122	likely_pathogenic	0.7367	pathogenic	-0.768	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	I
P/I	0.7165	likely_pathogenic	0.7903	pathogenic	-0.634	Destabilizing	0.997	D	0.811	deleterious	None	None	None	None	I
P/K	0.8614	likely_pathogenic	0.9164	pathogenic	-0.885	Destabilizing	0.999	D	0.799	deleterious	None	None	None	None	I
P/L	0.4417	ambiguous	0.5549	ambiguous	-0.634	Destabilizing	0.997	D	0.762	deleterious	D	0.527034222	None	None	I
P/M	0.6011	likely_pathogenic	0.7076	pathogenic	-0.425	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	I
P/N	0.8016	likely_pathogenic	0.8596	pathogenic	-0.505	Destabilizing	0.998	D	0.84	deleterious	None	None	None	None	I
P/Q	0.6085	likely_pathogenic	0.7291	pathogenic	-0.811	Destabilizing	0.999	D	0.833	deleterious	D	0.546912903	None	None	I
P/R	0.7757	likely_pathogenic	0.8579	pathogenic	-0.247	Destabilizing	1.0	D	0.845	deleterious	D	0.528301669	None	None	I
P/S	0.319	likely_benign	0.4039	ambiguous	-0.87	Destabilizing	0.997	D	0.755	deleterious	N	0.511411955	None	None	I
P/T	0.3871	ambiguous	0.4563	ambiguous	-0.877	Destabilizing	0.993	D	0.795	deleterious	N	0.520161368	None	None	I
P/V	0.5399	ambiguous	0.6294	pathogenic	-0.731	Destabilizing	0.993	D	0.768	deleterious	None	None	None	None	I
P/W	0.8706	likely_pathogenic	0.9309	pathogenic	-1.142	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	I
P/Y	0.7094	likely_pathogenic	0.8156	pathogenic	-0.886	Destabilizing	0.997	D	0.816	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.