TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9651	29176;29177;29178	chr2:178707616;178707615;178707614	chr2:179572343;179572342;179572341
N2AB	9334	28225;28226;28227	chr2:178707616;178707615;178707614	chr2:179572343;179572342;179572341
N2A	8407	25444;25445;25446	chr2:178707616;178707615;178707614	chr2:179572343;179572342;179572341
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-82
• Domain position: 62
• Structural Position: 143
• Q(SASA): 0.4991
• 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
D/E	None	None	None	None	0.087	0.049	0.0482279557977	gnomAD-4.0.0	2.40065E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62501E-06	0	0
D/N	None	None	None	None	0.109	0.088	0.0666544352282	gnomAD-4.0.0	2.73677E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59774E-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
D/A	0.1486	likely_benign	0.1143	benign	-0.184	Destabilizing	None	N	0.103	neutral	None	None	None	None	N
D/C	0.6428	likely_pathogenic	0.4958	ambiguous	0.069	Stabilizing	0.356	N	0.396	neutral	None	None	None	None	N
D/E	0.1291	likely_benign	0.1127	benign	-0.264	Destabilizing	None	N	0.087	neutral	None	None	None	None	N
D/F	0.5527	ambiguous	0.4386	ambiguous	-0.189	Destabilizing	0.356	N	0.434	neutral	None	None	None	None	N
D/G	0.1127	likely_benign	0.0962	benign	-0.364	Destabilizing	0.005	N	0.307	neutral	None	None	None	None	N
D/H	0.268	likely_benign	0.2065	benign	0.012	Stabilizing	0.295	N	0.316	neutral	None	None	None	None	N
D/I	0.4425	ambiguous	0.3268	benign	0.237	Stabilizing	0.072	N	0.457	neutral	None	None	None	None	N
D/K	0.3022	likely_benign	0.2436	benign	0.365	Stabilizing	0.016	N	0.332	neutral	None	None	None	None	N
D/L	0.3777	ambiguous	0.2906	benign	0.237	Stabilizing	0.031	N	0.337	neutral	None	None	None	None	N
D/M	0.5935	likely_pathogenic	0.476	ambiguous	0.315	Stabilizing	0.628	D	0.417	neutral	None	None	None	None	N
D/N	0.0904	likely_benign	0.0772	benign	0.14	Stabilizing	None	N	0.109	neutral	None	None	None	None	N
D/P	0.5711	likely_pathogenic	0.453	ambiguous	0.119	Stabilizing	None	N	0.107	neutral	None	None	None	None	N
D/Q	0.2859	likely_benign	0.2327	benign	0.151	Stabilizing	0.003	N	0.178	neutral	None	None	None	None	N
D/R	0.3501	ambiguous	0.2739	benign	0.523	Stabilizing	None	N	0.211	neutral	None	None	None	None	N
D/S	0.1214	likely_benign	0.1003	benign	0.017	Stabilizing	0.001	N	0.109	neutral	None	None	None	None	N
D/T	0.2516	likely_benign	0.188	benign	0.154	Stabilizing	0.031	N	0.315	neutral	None	None	None	None	N
D/V	0.2569	likely_benign	0.1869	benign	0.119	Stabilizing	0.012	N	0.365	neutral	None	None	None	None	N
D/W	0.8493	likely_pathogenic	0.7618	pathogenic	-0.089	Destabilizing	0.864	D	0.411	neutral	None	None	None	None	N
D/Y	0.2302	likely_benign	0.1814	benign	0.046	Stabilizing	0.56	D	0.449	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.