TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30477	91654;91655;91656	chr2:178551102;178551101;178551100	chr2:179415829;179415828;179415827
N2AB	28836	86731;86732;86733	chr2:178551102;178551101;178551100	chr2:179415829;179415828;179415827
N2A	27909	83950;83951;83952	chr2:178551102;178551101;178551100	chr2:179415829;179415828;179415827
N2B	21412	64459;64460;64461	chr2:178551102;178551101;178551100	chr2:179415829;179415828;179415827
Novex-1	21537	64834;64835;64836	chr2:178551102;178551101;178551100	chr2:179415829;179415828;179415827
Novex-2	21604	65035;65036;65037	chr2:178551102;178551101;178551100	chr2:179415829;179415828;179415827
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-110
• Domain position: 56
• Structural Position: 83
• Q(SASA): 0.5974
• 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
S/N	None	None	0.822	N	0.482	0.139	0.255270683199	gnomAD-4.0.0	6.84373E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.15974E-05	0
S/T	rs1699253758	None	0.014	N	0.199	0.092	0.183819452728	gnomAD-4.0.0	6.84373E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99593E-07	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
S/A	0.0689	likely_benign	0.0741	benign	-0.376	Destabilizing	0.559	D	0.364	neutral	None	None	None	None	I
S/C	0.1313	likely_benign	0.1389	benign	-0.415	Destabilizing	0.014	N	0.27	neutral	N	0.472978627	None	None	I
S/D	0.5151	ambiguous	0.5838	pathogenic	0.193	Stabilizing	0.86	D	0.447	neutral	None	None	None	None	I
S/E	0.5548	ambiguous	0.6243	pathogenic	0.117	Stabilizing	0.86	D	0.442	neutral	None	None	None	None	I
S/F	0.2264	likely_benign	0.2567	benign	-0.893	Destabilizing	0.978	D	0.609	neutral	None	None	None	None	I
S/G	0.0886	likely_benign	0.0953	benign	-0.507	Destabilizing	0.822	D	0.377	neutral	N	0.456798412	None	None	I
S/H	0.3773	ambiguous	0.4202	ambiguous	-0.897	Destabilizing	0.998	D	0.572	neutral	None	None	None	None	I
S/I	0.1516	likely_benign	0.162	benign	-0.158	Destabilizing	0.942	D	0.556	neutral	N	0.487427963	None	None	I
S/K	0.633	likely_pathogenic	0.7066	pathogenic	-0.525	Destabilizing	0.86	D	0.445	neutral	None	None	None	None	I
S/L	0.0802	likely_benign	0.0848	benign	-0.158	Destabilizing	0.754	D	0.493	neutral	None	None	None	None	I
S/M	0.141	likely_benign	0.1502	benign	-0.12	Destabilizing	0.994	D	0.569	neutral	None	None	None	None	I
S/N	0.1253	likely_benign	0.1316	benign	-0.303	Destabilizing	0.822	D	0.482	neutral	N	0.442887752	None	None	I
S/P	0.0918	likely_benign	0.1013	benign	-0.2	Destabilizing	0.978	D	0.567	neutral	None	None	None	None	I
S/Q	0.4233	ambiguous	0.4809	ambiguous	-0.495	Destabilizing	0.978	D	0.515	neutral	None	None	None	None	I
S/R	0.62	likely_pathogenic	0.6939	pathogenic	-0.309	Destabilizing	0.942	D	0.573	neutral	N	0.461145439	None	None	I
S/T	0.0666	likely_benign	0.0681	benign	-0.386	Destabilizing	0.014	N	0.199	neutral	N	0.405788014	None	None	I
S/V	0.1459	likely_benign	0.159	benign	-0.2	Destabilizing	0.754	D	0.524	neutral	None	None	None	None	I
S/W	0.4073	ambiguous	0.4635	ambiguous	-0.917	Destabilizing	0.998	D	0.674	neutral	None	None	None	None	I
S/Y	0.2393	likely_benign	0.2712	benign	-0.629	Destabilizing	0.993	D	0.616	neutral	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.