TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19203	57832;57833;57834	chr2:178595747;178595746;178595745	chr2:179460474;179460473;179460472
N2AB	17562	52909;52910;52911	chr2:178595747;178595746;178595745	chr2:179460474;179460473;179460472
N2A	16635	50128;50129;50130	chr2:178595747;178595746;178595745	chr2:179460474;179460473;179460472
N2B	10138	30637;30638;30639	chr2:178595747;178595746;178595745	chr2:179460474;179460473;179460472
Novex-1	10263	31012;31013;31014	chr2:178595747;178595746;178595745	chr2:179460474;179460473;179460472
Novex-2	10330	31213;31214;31215	chr2:178595747;178595746;178595745	chr2:179460474;179460473;179460472
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Fn3-27
• Domain position: 21
• Structural Position: 22
• Q(SASA): 0.0686
• 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
L/V	rs1170083550	-1.285	0.999	N	0.561	0.322	0.452928561435	gnomAD-2.1.1	4.13E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.13E-06	0
L/V	rs1170083550	-1.285	0.999	N	0.561	0.322	0.452928561435	gnomAD-4.0.0	1.60188E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.87208E-06	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
L/A	0.9628	likely_pathogenic	0.9726	pathogenic	-2.497	Highly Destabilizing	0.999	D	0.717	prob.delet.	None	None	None	None	N
L/C	0.9425	likely_pathogenic	0.9583	pathogenic	-1.85	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
L/D	0.9995	likely_pathogenic	0.9996	pathogenic	-3.384	Highly Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
L/E	0.997	likely_pathogenic	0.9979	pathogenic	-3.075	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
L/F	0.599	likely_pathogenic	0.6796	pathogenic	-1.452	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
L/G	0.9938	likely_pathogenic	0.9956	pathogenic	-3.081	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
L/H	0.9931	likely_pathogenic	0.9955	pathogenic	-2.912	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
L/I	0.1319	likely_benign	0.1527	benign	-0.737	Destabilizing	0.999	D	0.556	neutral	None	None	None	None	N
L/K	0.9949	likely_pathogenic	0.9965	pathogenic	-1.88	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
L/M	0.2734	likely_benign	0.3229	benign	-0.997	Destabilizing	1.0	D	0.717	prob.delet.	N	0.500425996	None	None	N
L/N	0.997	likely_pathogenic	0.9978	pathogenic	-2.572	Highly Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	N
L/P	0.9969	likely_pathogenic	0.998	pathogenic	-1.315	Destabilizing	1.0	D	0.913	deleterious	D	0.542510309	None	None	N
L/Q	0.9899	likely_pathogenic	0.9933	pathogenic	-2.233	Highly Destabilizing	1.0	D	0.911	deleterious	D	0.542510309	None	None	N
L/R	0.9914	likely_pathogenic	0.9941	pathogenic	-1.978	Destabilizing	1.0	D	0.892	deleterious	D	0.542510309	None	None	N
L/S	0.9963	likely_pathogenic	0.9977	pathogenic	-3.078	Highly Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
L/T	0.98	likely_pathogenic	0.9856	pathogenic	-2.613	Highly Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
L/V	0.2128	likely_benign	0.2467	benign	-1.315	Destabilizing	0.999	D	0.561	neutral	N	0.515019996	None	None	N
L/W	0.963	likely_pathogenic	0.9789	pathogenic	-1.949	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
L/Y	0.9599	likely_pathogenic	0.9754	pathogenic	-1.704	Destabilizing	1.0	D	0.815	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.