TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13909	41950;41951;41952	chr2:178635599;178635598;178635597	chr2:179500326;179500325;179500324
N2AB	12268	37027;37028;37029	chr2:178635599;178635598;178635597	chr2:179500326;179500325;179500324
N2A	11341	34246;34247;34248	chr2:178635599;178635598;178635597	chr2:179500326;179500325;179500324
N2B	4844	14755;14756;14757	chr2:178635599;178635598;178635597	chr2:179500326;179500325;179500324
Novex-1	4969	15130;15131;15132	chr2:178635599;178635598;178635597	chr2:179500326;179500325;179500324
Novex-2	5036	15331;15332;15333	chr2:178635599;178635598;178635597	chr2:179500326;179500325;179500324
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-89
• Domain position: 34
• Structural Position: 51
• Q(SASA): 0.2298
• 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/V	None	None	0.981	D	0.837	0.304	0.499535901811	gnomAD-4.0.0	6.93745E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.08473E-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	0.4203	ambiguous	0.339	benign	-0.26	Destabilizing	0.176	N	0.521	neutral	D	0.533320269	None	None	N
G/C	0.7543	likely_pathogenic	0.6058	pathogenic	-0.222	Destabilizing	0.999	D	0.786	deleterious	None	None	None	None	N
G/D	0.3385	likely_benign	0.2431	benign	-0.678	Destabilizing	0.996	D	0.855	deleterious	None	None	None	None	N
G/E	0.6231	likely_pathogenic	0.4625	ambiguous	-0.629	Destabilizing	0.99	D	0.857	deleterious	D	0.529697499	None	None	N
G/F	0.9425	likely_pathogenic	0.9083	pathogenic	-0.451	Destabilizing	0.999	D	0.848	deleterious	None	None	None	None	N
G/H	0.9163	likely_pathogenic	0.8375	pathogenic	-1.179	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
G/I	0.8762	likely_pathogenic	0.8019	pathogenic	0.409	Stabilizing	0.998	D	0.829	deleterious	None	None	None	None	N
G/K	0.9553	likely_pathogenic	0.9059	pathogenic	-0.566	Destabilizing	0.993	D	0.853	deleterious	None	None	None	None	N
G/L	0.868	likely_pathogenic	0.8083	pathogenic	0.409	Stabilizing	0.986	D	0.844	deleterious	None	None	None	None	N
G/M	0.9046	likely_pathogenic	0.8593	pathogenic	0.284	Stabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
G/N	0.4771	ambiguous	0.3645	ambiguous	-0.393	Destabilizing	0.996	D	0.81	deleterious	None	None	None	None	N
G/P	0.9903	likely_pathogenic	0.9842	pathogenic	0.229	Stabilizing	0.996	D	0.863	deleterious	None	None	None	None	N
G/Q	0.8678	likely_pathogenic	0.7698	pathogenic	-0.386	Destabilizing	0.999	D	0.863	deleterious	None	None	None	None	N
G/R	0.9204	likely_pathogenic	0.8427	pathogenic	-0.591	Destabilizing	0.99	D	0.869	deleterious	N	0.492084665	None	None	N
G/S	0.3145	likely_benign	0.2404	benign	-0.715	Destabilizing	0.986	D	0.769	deleterious	None	None	None	None	N
G/T	0.737	likely_pathogenic	0.6316	pathogenic	-0.568	Destabilizing	0.993	D	0.845	deleterious	None	None	None	None	N
G/V	0.8008	likely_pathogenic	0.6995	pathogenic	0.229	Stabilizing	0.981	D	0.837	deleterious	D	0.536981642	None	None	N
G/W	0.9135	likely_pathogenic	0.8552	pathogenic	-1.072	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
G/Y	0.8689	likely_pathogenic	0.7953	pathogenic	-0.467	Destabilizing	1.0	D	0.849	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.