TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20989	63190;63191;63192	chr2:178588760;178588759;178588758	chr2:179453487;179453486;179453485
N2AB	19348	58267;58268;58269	chr2:178588760;178588759;178588758	chr2:179453487;179453486;179453485
N2A	18421	55486;55487;55488	chr2:178588760;178588759;178588758	chr2:179453487;179453486;179453485
N2B	11924	35995;35996;35997	chr2:178588760;178588759;178588758	chr2:179453487;179453486;179453485
Novex-1	12049	36370;36371;36372	chr2:178588760;178588759;178588758	chr2:179453487;179453486;179453485
Novex-2	12116	36571;36572;36573	chr2:178588760;178588759;178588758	chr2:179453487;179453486;179453485
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-40
• Domain position: 27
• Structural Position: 29
• Q(SASA): 0.4845
• 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
Y/H	rs1338725751	0.295	0.994	N	0.461	0.19	0.269111216191	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.61E-05	None	0	None	0	0	0
Y/H	rs1338725751	0.295	0.994	N	0.461	0.19	0.269111216191	gnomAD-4.0.0	1.59226E-06	None	None	None	None	N	None	0	0	None	0	2.78149E-05	None	0	0	0	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
Y/A	0.4118	ambiguous	0.3515	ambiguous	-0.701	Destabilizing	0.985	D	0.545	neutral	None	None	None	None	N
Y/C	0.1726	likely_benign	0.1688	benign	0.034	Stabilizing	1.0	D	0.597	neutral	N	0.503893351	None	None	N
Y/D	0.1371	likely_benign	0.1228	benign	1.046	Stabilizing	0.925	D	0.562	neutral	N	0.370365932	None	None	N
Y/E	0.43	ambiguous	0.3762	ambiguous	1.027	Stabilizing	0.97	D	0.561	neutral	None	None	None	None	N
Y/F	0.1096	likely_benign	0.095	benign	-0.341	Destabilizing	0.993	D	0.447	neutral	N	0.417543803	None	None	N
Y/G	0.3748	ambiguous	0.3196	benign	-0.882	Destabilizing	0.97	D	0.544	neutral	None	None	None	None	N
Y/H	0.1648	likely_benign	0.1426	benign	0.21	Stabilizing	0.994	D	0.461	neutral	N	0.456966196	None	None	N
Y/I	0.4594	ambiguous	0.408	ambiguous	-0.255	Destabilizing	0.999	D	0.483	neutral	None	None	None	None	N
Y/K	0.3875	ambiguous	0.3372	benign	0.191	Stabilizing	0.97	D	0.549	neutral	None	None	None	None	N
Y/L	0.4838	ambiguous	0.4274	ambiguous	-0.255	Destabilizing	0.985	D	0.51	neutral	None	None	None	None	N
Y/M	0.5071	ambiguous	0.4496	ambiguous	-0.085	Destabilizing	1.0	D	0.489	neutral	None	None	None	None	N
Y/N	0.0851	likely_benign	0.0807	benign	0.003	Stabilizing	0.122	N	0.241	neutral	N	0.401054198	None	None	N
Y/P	0.931	likely_pathogenic	0.9192	pathogenic	-0.384	Destabilizing	0.999	D	0.596	neutral	None	None	None	None	N
Y/Q	0.3914	ambiguous	0.3352	benign	0.043	Stabilizing	0.996	D	0.499	neutral	None	None	None	None	N
Y/R	0.3485	ambiguous	0.2978	benign	0.459	Stabilizing	0.996	D	0.531	neutral	None	None	None	None	N
Y/S	0.1603	likely_benign	0.1395	benign	-0.475	Destabilizing	0.961	D	0.543	neutral	N	0.425219137	None	None	N
Y/T	0.284	likely_benign	0.233	benign	-0.405	Destabilizing	0.97	D	0.563	neutral	None	None	None	None	N
Y/V	0.3556	ambiguous	0.3082	benign	-0.384	Destabilizing	0.995	D	0.517	neutral	None	None	None	None	N
Y/W	0.4497	ambiguous	0.412	ambiguous	-0.444	Destabilizing	1.0	D	0.433	neutral	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.