TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29565	88918;88919;88920	chr2:178554654;178554653;178554652	chr2:179419381;179419380;179419379
N2AB	27924	83995;83996;83997	chr2:178554654;178554653;178554652	chr2:179419381;179419380;179419379
N2A	26997	81214;81215;81216	chr2:178554654;178554653;178554652	chr2:179419381;179419380;179419379
N2B	20500	61723;61724;61725	chr2:178554654;178554653;178554652	chr2:179419381;179419380;179419379
Novex-1	20625	62098;62099;62100	chr2:178554654;178554653;178554652	chr2:179419381;179419380;179419379
Novex-2	20692	62299;62300;62301	chr2:178554654;178554653;178554652	chr2:179419381;179419380;179419379
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-103
• Domain position: 33
• Structural Position: 34
• Q(SASA): 0.8299
• 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/T	rs1263180064	0.189	0.183	N	0.423	0.158	0.216624796971	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
K/T	rs1263180064	0.189	0.183	N	0.423	0.158	0.216624796971	gnomAD-4.0.0	4.77307E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	4.29824E-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
K/A	0.1636	likely_benign	0.16	benign	0.045	Stabilizing	0.061	N	0.363	neutral	None	None	None	None	N
K/C	0.5148	ambiguous	0.5363	ambiguous	-0.154	Destabilizing	0.983	D	0.497	neutral	None	None	None	None	N
K/D	0.286	likely_benign	0.2819	benign	-0.026	Destabilizing	0.264	N	0.451	neutral	None	None	None	None	N
K/E	0.1087	likely_benign	0.1105	benign	-0.024	Destabilizing	0.183	N	0.276	neutral	N	0.40492401	None	None	N
K/F	0.6316	likely_pathogenic	0.6531	pathogenic	-0.179	Destabilizing	0.716	D	0.54	neutral	None	None	None	None	N
K/G	0.2667	likely_benign	0.2864	benign	-0.146	Destabilizing	0.129	N	0.485	neutral	None	None	None	None	N
K/H	0.2484	likely_benign	0.25	benign	-0.389	Destabilizing	0.836	D	0.445	neutral	None	None	None	None	N
K/I	0.2437	likely_benign	0.2503	benign	0.465	Stabilizing	0.101	N	0.505	neutral	N	0.47134379	None	None	N
K/L	0.2438	likely_benign	0.2517	benign	0.465	Stabilizing	0.061	N	0.413	neutral	None	None	None	None	N
K/M	0.1757	likely_benign	0.1784	benign	0.223	Stabilizing	0.012	N	0.151	neutral	None	None	None	None	N
K/N	0.2143	likely_benign	0.2097	benign	0.249	Stabilizing	0.002	N	0.147	neutral	N	0.46489782	None	None	N
K/P	0.2412	likely_benign	0.2459	benign	0.353	Stabilizing	0.001	N	0.115	neutral	None	None	None	None	N
K/Q	0.1085	likely_benign	0.1079	benign	0.08	Stabilizing	0.351	N	0.352	neutral	N	0.461857515	None	None	N
K/R	0.0794	likely_benign	0.0844	benign	-0.009	Destabilizing	0.002	N	0.118	neutral	N	0.452584671	None	None	N
K/S	0.223	likely_benign	0.2124	benign	-0.196	Destabilizing	0.129	N	0.24	neutral	None	None	None	None	N
K/T	0.1188	likely_benign	0.1122	benign	-0.052	Destabilizing	0.183	N	0.423	neutral	N	0.450101726	None	None	N
K/V	0.1949	likely_benign	0.2024	benign	0.353	Stabilizing	0.001	N	0.134	neutral	None	None	None	None	N
K/W	0.6587	likely_pathogenic	0.7067	pathogenic	-0.22	Destabilizing	0.983	D	0.488	neutral	None	None	None	None	N
K/Y	0.5036	ambiguous	0.5298	ambiguous	0.135	Stabilizing	0.94	D	0.53	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.