TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2624	8095;8096;8097	chr2:178771457;178771456;178771455	chr2:179636184;179636183;179636182
N2AB	2624	8095;8096;8097	chr2:178771457;178771456;178771455	chr2:179636184;179636183;179636182
N2A	2624	8095;8096;8097	chr2:178771457;178771456;178771455	chr2:179636184;179636183;179636182
N2B	2578	7957;7958;7959	chr2:178771457;178771456;178771455	chr2:179636184;179636183;179636182
Novex-1	2578	7957;7958;7959	chr2:178771457;178771456;178771455	chr2:179636184;179636183;179636182
Novex-2	2578	7957;7958;7959	chr2:178771457;178771456;178771455	chr2:179636184;179636183;179636182
Novex-3	2624	8095;8096;8097	chr2:178771457;178771456;178771455	chr2:179636184;179636183;179636182

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-16
• Domain position: 4
• Structural Position: 5
• Q(SASA): 0.4628
• 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
K/Q	None	None	0.002	N	0.133	0.128	0.119812018005	gnomAD-4.0.0	1.59111E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43287E-05	0
K/R	rs1163440648	None	None	N	0.138	0.124	0.207176502487	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/R	rs1163440648	None	None	N	0.138	0.124	0.207176502487	gnomAD-4.0.0	5.07456E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.02458E-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
K/A	0.4098	ambiguous	0.4284	ambiguous	-0.182	Destabilizing	0.035	N	0.355	neutral	None	None	None	None	N
K/C	0.7199	likely_pathogenic	0.7112	pathogenic	-0.279	Destabilizing	0.824	D	0.429	neutral	None	None	None	None	N
K/D	0.7361	likely_pathogenic	0.7601	pathogenic	-0.13	Destabilizing	0.149	N	0.404	neutral	None	None	None	None	N
K/E	0.2225	likely_benign	0.24	benign	-0.079	Destabilizing	0.027	N	0.377	neutral	N	0.505749689	None	None	N
K/F	0.723	likely_pathogenic	0.7235	pathogenic	-0.074	Destabilizing	0.555	D	0.427	neutral	None	None	None	None	N
K/G	0.6014	likely_pathogenic	0.6174	pathogenic	-0.48	Destabilizing	0.149	N	0.393	neutral	None	None	None	None	N
K/H	0.3088	likely_benign	0.3068	benign	-0.834	Destabilizing	0.555	D	0.401	neutral	None	None	None	None	N
K/I	0.2792	likely_benign	0.2782	benign	0.555	Stabilizing	0.235	N	0.441	neutral	None	None	None	None	N
K/L	0.3413	ambiguous	0.3518	ambiguous	0.555	Stabilizing	0.081	N	0.401	neutral	None	None	None	None	N
K/M	0.2453	likely_benign	0.2475	benign	0.362	Stabilizing	0.484	N	0.401	neutral	D	0.555001522	None	None	N
K/N	0.4345	ambiguous	0.4642	ambiguous	-0.127	Destabilizing	0.117	N	0.349	neutral	D	0.584273782	None	None	N
K/P	0.9644	likely_pathogenic	0.9586	pathogenic	0.34	Stabilizing	0.555	D	0.409	neutral	None	None	None	None	N
K/Q	0.1412	likely_benign	0.1465	benign	-0.264	Destabilizing	0.002	N	0.133	neutral	N	0.48099249	None	None	N
K/R	0.0895	likely_benign	0.0888	benign	-0.39	Destabilizing	None	N	0.138	neutral	N	0.462307258	None	None	N
K/S	0.4587	ambiguous	0.4811	ambiguous	-0.639	Destabilizing	0.035	N	0.33	neutral	None	None	None	None	N
K/T	0.1826	likely_benign	0.1934	benign	-0.413	Destabilizing	None	N	0.284	neutral	N	0.507714891	None	None	N
K/V	0.2726	likely_benign	0.2766	benign	0.34	Stabilizing	0.081	N	0.419	neutral	None	None	None	None	N
K/W	0.8136	likely_pathogenic	0.799	pathogenic	-0.02	Destabilizing	0.935	D	0.453	neutral	None	None	None	None	N
K/Y	0.6208	likely_pathogenic	0.6197	pathogenic	0.281	Stabilizing	0.555	D	0.427	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.