TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5049	15370;15371;15372	chr2:178734779;178734778;178734777	chr2:179599506;179599505;179599504
N2AB	4732	14419;14420;14421	chr2:178734779;178734778;178734777	chr2:179599506;179599505;179599504
N2A	3805	11638;11639;11640	chr2:178734779;178734778;178734777	chr2:179599506;179599505;179599504
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-33
• Domain position: 69
• Structural Position: 151
• Q(SASA): 0.2127
• 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
S/G	None	None	0.939	N	0.437	0.346	0.454518106513	gnomAD-4.0.0	1.5913E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85838E-06	0	0
S/N	rs1314741857	-0.438	0.939	D	0.491	0.26	0.429320821379	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
S/N	rs1314741857	-0.438	0.939	D	0.491	0.26	0.429320821379	gnomAD-4.0.0	4.77432E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	4.30046E-05	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
S/A	0.1196	likely_benign	0.1109	benign	-0.79	Destabilizing	0.807	D	0.371	neutral	None	None	None	None	N
S/C	0.2918	likely_benign	0.2589	benign	-0.522	Destabilizing	0.999	D	0.759	deleterious	D	0.668875497	None	None	N
S/D	0.8206	likely_pathogenic	0.7902	pathogenic	-0.005	Destabilizing	0.953	D	0.49	neutral	None	None	None	None	N
S/E	0.8402	likely_pathogenic	0.8102	pathogenic	-0.006	Destabilizing	0.953	D	0.488	neutral	None	None	None	None	N
S/F	0.6805	likely_pathogenic	0.6225	pathogenic	-0.981	Destabilizing	0.993	D	0.829	deleterious	None	None	None	None	N
S/G	0.1432	likely_benign	0.1147	benign	-1.031	Destabilizing	0.939	D	0.437	neutral	N	0.513497879	None	None	N
S/H	0.7952	likely_pathogenic	0.7417	pathogenic	-1.471	Destabilizing	0.999	D	0.756	deleterious	None	None	None	None	N
S/I	0.6107	likely_pathogenic	0.4908	ambiguous	-0.255	Destabilizing	0.982	D	0.796	deleterious	D	0.636906446	None	None	N
S/K	0.9227	likely_pathogenic	0.8974	pathogenic	-0.586	Destabilizing	0.953	D	0.485	neutral	None	None	None	None	N
S/L	0.2844	likely_benign	0.2556	benign	-0.255	Destabilizing	0.91	D	0.61	neutral	None	None	None	None	N
S/M	0.4509	ambiguous	0.3965	ambiguous	-0.008	Destabilizing	0.999	D	0.759	deleterious	None	None	None	None	N
S/N	0.4175	ambiguous	0.347	ambiguous	-0.534	Destabilizing	0.939	D	0.491	neutral	D	0.566565108	None	None	N
S/P	0.9289	likely_pathogenic	0.9184	pathogenic	-0.4	Destabilizing	0.993	D	0.757	deleterious	None	None	None	None	N
S/Q	0.8292	likely_pathogenic	0.7794	pathogenic	-0.686	Destabilizing	0.993	D	0.648	neutral	None	None	None	None	N
S/R	0.8666	likely_pathogenic	0.8126	pathogenic	-0.513	Destabilizing	0.991	D	0.775	deleterious	D	0.578555302	None	None	N
S/T	0.1353	likely_benign	0.1408	benign	-0.607	Destabilizing	0.17	N	0.364	neutral	N	0.512190895	None	None	N
S/V	0.5769	likely_pathogenic	0.4903	ambiguous	-0.4	Destabilizing	0.973	D	0.69	prob.neutral	None	None	None	None	N
S/W	0.8311	likely_pathogenic	0.799	pathogenic	-0.925	Destabilizing	0.999	D	0.788	deleterious	None	None	None	None	N
S/Y	0.6248	likely_pathogenic	0.5862	pathogenic	-0.665	Destabilizing	0.998	D	0.821	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.