TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14325	43198;43199;43200	chr2:178633300;178633299;178633298	chr2:179498027;179498026;179498025
N2AB	12684	38275;38276;38277	chr2:178633300;178633299;178633298	chr2:179498027;179498026;179498025
N2A	11757	35494;35495;35496	chr2:178633300;178633299;178633298	chr2:179498027;179498026;179498025
N2B	5260	16003;16004;16005	chr2:178633300;178633299;178633298	chr2:179498027;179498026;179498025
Novex-1	5385	16378;16379;16380	chr2:178633300;178633299;178633298	chr2:179498027;179498026;179498025
Novex-2	5452	16579;16580;16581	chr2:178633300;178633299;178633298	chr2:179498027;179498026;179498025
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: Ig-94
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.0969
• 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/P	rs979749249	-1.136	0.998	D	0.835	0.478	0.610312411291	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	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	0.8931	likely_pathogenic	0.8975	pathogenic	-2.123	Highly Destabilizing	0.964	D	0.619	neutral	None	None	None	None	N
L/C	0.9297	likely_pathogenic	0.9355	pathogenic	-1.331	Destabilizing	1.0	D	0.725	deleterious	None	None	None	None	N
L/D	0.9981	likely_pathogenic	0.9984	pathogenic	-2.217	Highly Destabilizing	0.998	D	0.835	deleterious	None	None	None	None	N
L/E	0.9892	likely_pathogenic	0.9918	pathogenic	-1.971	Destabilizing	0.998	D	0.849	deleterious	None	None	None	None	N
L/F	0.818	likely_pathogenic	0.8222	pathogenic	-1.153	Destabilizing	0.99	D	0.742	deleterious	None	None	None	None	N
L/G	0.9835	likely_pathogenic	0.9862	pathogenic	-2.682	Highly Destabilizing	0.995	D	0.853	deleterious	None	None	None	None	N
L/H	0.9815	likely_pathogenic	0.9865	pathogenic	-2.216	Highly Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
L/I	0.284	likely_benign	0.2563	benign	-0.512	Destabilizing	0.455	N	0.325	neutral	None	None	None	None	N
L/K	0.9837	likely_pathogenic	0.9885	pathogenic	-1.447	Destabilizing	0.995	D	0.822	deleterious	None	None	None	None	N
L/M	0.4375	ambiguous	0.3959	ambiguous	-0.549	Destabilizing	0.647	D	0.343	neutral	N	0.439067303	None	None	N
L/N	0.9848	likely_pathogenic	0.9874	pathogenic	-1.81	Destabilizing	0.998	D	0.829	deleterious	None	None	None	None	N
L/P	0.9323	likely_pathogenic	0.9538	pathogenic	-1.029	Destabilizing	0.998	D	0.835	deleterious	D	0.610592339	None	None	N
L/Q	0.9584	likely_pathogenic	0.9667	pathogenic	-1.611	Destabilizing	0.993	D	0.78	deleterious	D	0.624485567	None	None	N
L/R	0.9599	likely_pathogenic	0.9756	pathogenic	-1.363	Destabilizing	0.993	D	0.792	deleterious	D	0.623658585	None	None	N
L/S	0.9735	likely_pathogenic	0.9762	pathogenic	-2.517	Highly Destabilizing	0.995	D	0.804	deleterious	None	None	None	None	N
L/T	0.9241	likely_pathogenic	0.9304	pathogenic	-2.119	Highly Destabilizing	0.995	D	0.729	deleterious	None	None	None	None	N
L/V	0.3495	ambiguous	0.3408	ambiguous	-1.029	Destabilizing	0.807	D	0.554	neutral	D	0.582627258	None	None	N
L/W	0.976	likely_pathogenic	0.9804	pathogenic	-1.55	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
L/Y	0.9842	likely_pathogenic	0.9869	pathogenic	-1.193	Destabilizing	0.998	D	0.711	prob.delet.	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.