TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23488	70687;70688;70689	chr2:178575670;178575669;178575668	chr2:179440397;179440396;179440395
N2AB	21847	65764;65765;65766	chr2:178575670;178575669;178575668	chr2:179440397;179440396;179440395
N2A	20920	62983;62984;62985	chr2:178575670;178575669;178575668	chr2:179440397;179440396;179440395
N2B	14423	43492;43493;43494	chr2:178575670;178575669;178575668	chr2:179440397;179440396;179440395
Novex-1	14548	43867;43868;43869	chr2:178575670;178575669;178575668	chr2:179440397;179440396;179440395
Novex-2	14615	44068;44069;44070	chr2:178575670;178575669;178575668	chr2:179440397;179440396;179440395
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-58
• Domain position: 54
• Structural Position: 75
• Q(SASA): 0.6924
• 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/E	None	None	0.166	N	0.132	0.215	0.197625483188	gnomAD-4.0.0	1.36858E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.7991E-06	0	0
K/R	None	None	0.166	N	0.162	0.106	0.166414681773	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.253	likely_benign	0.2694	benign	0.109	Stabilizing	0.007	N	0.117	neutral	None	None	None	None	N
K/C	0.6132	likely_pathogenic	0.6112	pathogenic	0.186	Stabilizing	0.965	D	0.242	neutral	None	None	None	None	N
K/D	0.4141	ambiguous	0.4272	ambiguous	-0.026	Destabilizing	0.209	N	0.223	neutral	None	None	None	None	N
K/E	0.1988	likely_benign	0.2206	benign	-0.027	Destabilizing	0.166	N	0.132	neutral	N	0.445349267	None	None	N
K/F	0.7742	likely_pathogenic	0.8024	pathogenic	-0.092	Destabilizing	0.965	D	0.293	neutral	None	None	None	None	N
K/G	0.3594	ambiguous	0.3645	ambiguous	-0.082	Destabilizing	0.103	N	0.211	neutral	None	None	None	None	N
K/H	0.2411	likely_benign	0.2487	benign	-0.37	Destabilizing	0.901	D	0.259	neutral	None	None	None	None	N
K/I	0.4142	ambiguous	0.4691	ambiguous	0.54	Stabilizing	0.561	D	0.361	neutral	None	None	None	None	N
K/L	0.3825	ambiguous	0.4207	ambiguous	0.54	Stabilizing	0.345	N	0.203	neutral	None	None	None	None	N
K/M	0.2762	likely_benign	0.3125	benign	0.324	Stabilizing	0.873	D	0.257	neutral	N	0.483765501	None	None	N
K/N	0.2689	likely_benign	0.3016	benign	0.584	Stabilizing	0.001	N	0.157	neutral	N	0.425648785	None	None	N
K/P	0.8299	likely_pathogenic	0.8363	pathogenic	0.423	Stabilizing	0.722	D	0.275	neutral	None	None	None	None	N
K/Q	0.1246	likely_benign	0.1313	benign	0.401	Stabilizing	0.013	N	0.163	neutral	N	0.491276345	None	None	N
K/R	0.0824	likely_benign	0.081	benign	0.159	Stabilizing	0.166	N	0.162	neutral	N	0.494065934	None	None	N
K/S	0.2794	likely_benign	0.2969	benign	0.184	Stabilizing	0.021	N	0.147	neutral	None	None	None	None	N
K/T	0.1418	likely_benign	0.1606	benign	0.316	Stabilizing	0.002	N	0.105	neutral	N	0.451179161	None	None	N
K/V	0.3117	likely_benign	0.3465	ambiguous	0.423	Stabilizing	0.345	N	0.21	neutral	None	None	None	None	N
K/W	0.7889	likely_pathogenic	0.8085	pathogenic	-0.149	Destabilizing	0.991	D	0.237	neutral	None	None	None	None	N
K/Y	0.5781	likely_pathogenic	0.6153	pathogenic	0.194	Stabilizing	0.965	D	0.315	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.