TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24657	74194;74195;74196	chr2:178572163;178572162;178572161	chr2:179436890;179436889;179436888
N2AB	23016	69271;69272;69273	chr2:178572163;178572162;178572161	chr2:179436890;179436889;179436888
N2A	22089	66490;66491;66492	chr2:178572163;178572162;178572161	chr2:179436890;179436889;179436888
N2B	15592	46999;47000;47001	chr2:178572163;178572162;178572161	chr2:179436890;179436889;179436888
Novex-1	15717	47374;47375;47376	chr2:178572163;178572162;178572161	chr2:179436890;179436889;179436888
Novex-2	15784	47575;47576;47577	chr2:178572163;178572162;178572161	chr2:179436890;179436889;179436888
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-67
• Domain position: 42
• Structural Position: 44
• Q(SASA): 0.189
• 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
T/P	None	None	0.011	N	0.405	0.117	0.194818534648	gnomAD-4.0.0	1.59207E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85928E-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
T/A	0.0652	likely_benign	0.059	benign	-1.021	Destabilizing	None	N	0.079	neutral	N	0.453334032	None	None	N
T/C	0.2343	likely_benign	0.2154	benign	-0.604	Destabilizing	0.266	N	0.346	neutral	None	None	None	None	N
T/D	0.539	ambiguous	0.4641	ambiguous	-0.056	Destabilizing	0.003	N	0.351	neutral	None	None	None	None	N
T/E	0.4112	ambiguous	0.3602	ambiguous	-0.06	Destabilizing	0.01	N	0.388	neutral	None	None	None	None	N
T/F	0.3449	ambiguous	0.2781	benign	-1.197	Destabilizing	0.155	N	0.443	neutral	None	None	None	None	N
T/G	0.1148	likely_benign	0.1013	benign	-1.259	Destabilizing	None	N	0.15	neutral	None	None	None	None	N
T/H	0.2997	likely_benign	0.2597	benign	-1.526	Destabilizing	0.327	N	0.425	neutral	None	None	None	None	N
T/I	0.2127	likely_benign	0.1786	benign	-0.477	Destabilizing	None	N	0.138	neutral	N	0.477808402	None	None	N
T/K	0.2843	likely_benign	0.253	benign	-0.646	Destabilizing	0.006	N	0.336	neutral	None	None	None	None	N
T/L	0.1095	likely_benign	0.0897	benign	-0.477	Destabilizing	0.002	N	0.267	neutral	None	None	None	None	N
T/M	0.1037	likely_benign	0.0934	benign	-0.112	Destabilizing	0.194	N	0.343	neutral	None	None	None	None	N
T/N	0.1098	likely_benign	0.0998	benign	-0.549	Destabilizing	0.002	N	0.27	neutral	N	0.471746435	None	None	N
T/P	0.0683	likely_benign	0.0622	benign	-0.628	Destabilizing	0.011	N	0.405	neutral	N	0.420354822	None	None	N
T/Q	0.2307	likely_benign	0.2133	benign	-0.746	Destabilizing	0.031	N	0.389	neutral	None	None	None	None	N
T/R	0.2597	likely_benign	0.2267	benign	-0.418	Destabilizing	None	N	0.133	neutral	None	None	None	None	N
T/S	0.0768	likely_benign	0.0716	benign	-0.905	Destabilizing	None	N	0.067	neutral	N	0.423915202	None	None	N
T/V	0.1505	likely_benign	0.1319	benign	-0.628	Destabilizing	0.002	N	0.233	neutral	None	None	None	None	N
T/W	0.6337	likely_pathogenic	0.5392	ambiguous	-1.063	Destabilizing	0.937	D	0.385	neutral	None	None	None	None	N
T/Y	0.3089	likely_benign	0.2483	benign	-0.843	Destabilizing	0.271	N	0.429	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.