TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28518	85777;85778;85779	chr2:178560580;178560579;178560578	chr2:179425307;179425306;179425305
N2AB	26877	80854;80855;80856	chr2:178560580;178560579;178560578	chr2:179425307;179425306;179425305
N2A	25950	78073;78074;78075	chr2:178560580;178560579;178560578	chr2:179425307;179425306;179425305
N2B	19453	58582;58583;58584	chr2:178560580;178560579;178560578	chr2:179425307;179425306;179425305
Novex-1	19578	58957;58958;58959	chr2:178560580;178560579;178560578	chr2:179425307;179425306;179425305
Novex-2	19645	59158;59159;59160	chr2:178560580;178560579;178560578	chr2:179425307;179425306;179425305
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: Fn3-95
• Domain position: 69
• Structural Position: 100
• Q(SASA): 0.2575
• 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
G/D	rs1464682626	-1.399	1.0	N	0.804	0.446	0.327686398923	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	2.87853E-04	0	0
G/D	rs1464682626	-1.399	1.0	N	0.804	0.446	0.327686398923	gnomAD-4.0.0	2.73779E-06	None	None	None	None	N	None	0	0	None	0	0	None	5.63804E-05	0	8.99549E-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
G/A	0.5382	ambiguous	0.5828	pathogenic	-0.48	Destabilizing	1.0	D	0.716	prob.delet.	N	0.508473711	None	None	N
G/C	0.5276	ambiguous	0.6001	pathogenic	-0.807	Destabilizing	1.0	D	0.801	deleterious	D	0.553787255	None	None	N
G/D	0.2496	likely_benign	0.2994	benign	-0.88	Destabilizing	1.0	D	0.804	deleterious	N	0.480961707	None	None	N
G/E	0.4523	ambiguous	0.4993	ambiguous	-1.016	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
G/F	0.9012	likely_pathogenic	0.9203	pathogenic	-1.038	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
G/H	0.7312	likely_pathogenic	0.7625	pathogenic	-0.861	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
G/I	0.8906	likely_pathogenic	0.9156	pathogenic	-0.424	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
G/K	0.805	likely_pathogenic	0.8294	pathogenic	-1.13	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
G/L	0.8806	likely_pathogenic	0.901	pathogenic	-0.424	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
G/M	0.8696	likely_pathogenic	0.8897	pathogenic	-0.368	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
G/N	0.3231	likely_benign	0.3299	benign	-0.684	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
G/P	0.9862	likely_pathogenic	0.991	pathogenic	-0.405	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
G/Q	0.6742	likely_pathogenic	0.7	pathogenic	-0.966	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
G/R	0.7152	likely_pathogenic	0.7499	pathogenic	-0.65	Destabilizing	1.0	D	0.834	deleterious	D	0.526021761	None	None	N
G/S	0.2467	likely_benign	0.2646	benign	-0.849	Destabilizing	1.0	D	0.79	deleterious	N	0.518816058	None	None	N
G/T	0.5846	likely_pathogenic	0.6339	pathogenic	-0.919	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
G/V	0.7916	likely_pathogenic	0.834	pathogenic	-0.405	Destabilizing	1.0	D	0.819	deleterious	D	0.54192397	None	None	N
G/W	0.7173	likely_pathogenic	0.7689	pathogenic	-1.261	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
G/Y	0.7228	likely_pathogenic	0.7647	pathogenic	-0.906	Destabilizing	1.0	D	0.79	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.