TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15326	46201;46202;46203	chr2:178620545;178620544;178620543	chr2:179485272;179485271;179485270
N2AB	13685	41278;41279;41280	chr2:178620545;178620544;178620543	chr2:179485272;179485271;179485270
N2A	12758	38497;38498;38499	chr2:178620545;178620544;178620543	chr2:179485272;179485271;179485270
N2B	6261	19006;19007;19008	chr2:178620545;178620544;178620543	chr2:179485272;179485271;179485270
Novex-1	6386	19381;19382;19383	chr2:178620545;178620544;178620543	chr2:179485272;179485271;179485270
Novex-2	6453	19582;19583;19584	chr2:178620545;178620544;178620543	chr2:179485272;179485271;179485270
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-105
• Domain position: 25
• Structural Position: 38
• Q(SASA): 0.5683
• 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
N/K	None	None	1.0	N	0.657	0.341	0.256793551483	gnomAD-4.0.0	6.84882E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.65898E-05
N/S	rs2058104840	None	0.999	N	0.491	0.452	0.276898752692	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
N/S	rs2058104840	None	0.999	N	0.491	0.452	0.276898752692	gnomAD-4.0.0	6.58059E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.4728E-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
N/A	0.925	likely_pathogenic	0.8238	pathogenic	-0.662	Destabilizing	1.0	D	0.625	neutral	None	None	None	None	N
N/C	0.936	likely_pathogenic	0.8733	pathogenic	0.01	Stabilizing	1.0	D	0.663	neutral	None	None	None	None	N
N/D	0.6037	likely_pathogenic	0.5075	ambiguous	0.053	Stabilizing	0.999	D	0.55	neutral	N	0.507216827	None	None	N
N/E	0.9648	likely_pathogenic	0.9232	pathogenic	0.138	Stabilizing	0.999	D	0.641	neutral	None	None	None	None	N
N/F	0.9882	likely_pathogenic	0.9682	pathogenic	-0.56	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	N
N/G	0.8766	likely_pathogenic	0.7864	pathogenic	-0.962	Destabilizing	0.999	D	0.495	neutral	None	None	None	None	N
N/H	0.8233	likely_pathogenic	0.6239	pathogenic	-0.581	Destabilizing	1.0	D	0.639	neutral	D	0.607530484	None	None	N
N/I	0.9294	likely_pathogenic	0.836	pathogenic	0.085	Stabilizing	1.0	D	0.693	prob.neutral	D	0.605175548	None	None	N
N/K	0.9819	likely_pathogenic	0.9334	pathogenic	-0.031	Destabilizing	1.0	D	0.657	neutral	N	0.505191964	None	None	N
N/L	0.9186	likely_pathogenic	0.8222	pathogenic	0.085	Stabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	N
N/M	0.9493	likely_pathogenic	0.8943	pathogenic	0.18	Stabilizing	1.0	D	0.603	neutral	None	None	None	None	N
N/P	0.9626	likely_pathogenic	0.9286	pathogenic	-0.135	Destabilizing	1.0	D	0.67	neutral	None	None	None	None	N
N/Q	0.9598	likely_pathogenic	0.9033	pathogenic	-0.514	Destabilizing	1.0	D	0.646	neutral	None	None	None	None	N
N/R	0.9727	likely_pathogenic	0.9132	pathogenic	-0.03	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
N/S	0.2746	likely_benign	0.1921	benign	-0.644	Destabilizing	0.999	D	0.491	neutral	N	0.438261818	None	None	N
N/T	0.6742	likely_pathogenic	0.4905	ambiguous	-0.368	Destabilizing	0.999	D	0.637	neutral	N	0.503435424	None	None	N
N/V	0.9337	likely_pathogenic	0.8427	pathogenic	-0.135	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	N
N/W	0.9937	likely_pathogenic	0.9861	pathogenic	-0.396	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	N
N/Y	0.8884	likely_pathogenic	0.7528	pathogenic	-0.147	Destabilizing	1.0	D	0.648	neutral	D	0.607662234	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.