TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29692	89299;89300;89301	chr2:178554037;178554036;178554035	chr2:179418764;179418763;179418762
N2AB	28051	84376;84377;84378	chr2:178554037;178554036;178554035	chr2:179418764;179418763;179418762
N2A	27124	81595;81596;81597	chr2:178554037;178554036;178554035	chr2:179418764;179418763;179418762
N2B	20627	62104;62105;62106	chr2:178554037;178554036;178554035	chr2:179418764;179418763;179418762
Novex-1	20752	62479;62480;62481	chr2:178554037;178554036;178554035	chr2:179418764;179418763;179418762
Novex-2	20819	62680;62681;62682	chr2:178554037;178554036;178554035	chr2:179418764;179418763;179418762
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-104
• Domain position: 60
• Structural Position: 90
• Q(SASA): 0.3612
• 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
R/K	rs745523889	-0.685	0.997	N	0.489	0.243	0.259272394797	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	8.89E-06	0
R/K	rs745523889	-0.685	0.997	N	0.489	0.243	0.259272394797	gnomAD-4.0.0	6.1581E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69835E-06	6.95604E-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
R/A	0.8959	likely_pathogenic	0.9127	pathogenic	-0.308	Destabilizing	0.999	D	0.611	neutral	None	None	None	None	N
R/C	0.3964	ambiguous	0.4543	ambiguous	-0.416	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
R/D	0.9718	likely_pathogenic	0.9778	pathogenic	0.068	Stabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
R/E	0.8355	likely_pathogenic	0.8494	pathogenic	0.182	Stabilizing	0.999	D	0.669	neutral	None	None	None	None	N
R/F	0.8869	likely_pathogenic	0.9065	pathogenic	-0.252	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
R/G	0.8157	likely_pathogenic	0.8596	pathogenic	-0.583	Destabilizing	1.0	D	0.716	prob.delet.	N	0.485638379	None	None	N
R/H	0.2768	likely_benign	0.3122	benign	-0.976	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
R/I	0.7559	likely_pathogenic	0.7616	pathogenic	0.408	Stabilizing	1.0	D	0.805	deleterious	N	0.51532664	None	None	N
R/K	0.3246	likely_benign	0.3349	benign	-0.315	Destabilizing	0.997	D	0.489	neutral	N	0.5023387	None	None	N
R/L	0.7418	likely_pathogenic	0.7648	pathogenic	0.408	Stabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	N
R/M	0.794	likely_pathogenic	0.8056	pathogenic	-0.11	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
R/N	0.9356	likely_pathogenic	0.945	pathogenic	-0.029	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
R/P	0.9877	likely_pathogenic	0.9905	pathogenic	0.191	Stabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
R/Q	0.2892	likely_benign	0.3073	benign	-0.107	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
R/S	0.8939	likely_pathogenic	0.9125	pathogenic	-0.586	Destabilizing	1.0	D	0.777	deleterious	N	0.427491438	None	None	N
R/T	0.7404	likely_pathogenic	0.7519	pathogenic	-0.301	Destabilizing	1.0	D	0.763	deleterious	N	0.456352908	None	None	N
R/V	0.798	likely_pathogenic	0.8059	pathogenic	0.191	Stabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
R/W	0.4298	ambiguous	0.4965	ambiguous	-0.107	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
R/Y	0.7334	likely_pathogenic	0.7729	pathogenic	0.241	Stabilizing	1.0	D	0.819	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.