TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30488	91687;91688;91689	chr2:178551069;178551068;178551067	chr2:179415796;179415795;179415794
N2AB	28847	86764;86765;86766	chr2:178551069;178551068;178551067	chr2:179415796;179415795;179415794
N2A	27920	83983;83984;83985	chr2:178551069;178551068;178551067	chr2:179415796;179415795;179415794
N2B	21423	64492;64493;64494	chr2:178551069;178551068;178551067	chr2:179415796;179415795;179415794
Novex-1	21548	64867;64868;64869	chr2:178551069;178551068;178551067	chr2:179415796;179415795;179415794
Novex-2	21615	65068;65069;65070	chr2:178551069;178551068;178551067	chr2:179415796;179415795;179415794
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-110
• Domain position: 67
• Structural Position: 99
• Q(SASA): 0.3284
• 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
P/L	rs868503876	None	0.896	N	0.56	0.539	0.664074601257	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	0	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
P/A	0.0625	likely_benign	0.0661	benign	-0.516	Destabilizing	0.046	N	0.235	neutral	N	0.494162253	None	None	N
P/C	0.4886	ambiguous	0.5669	pathogenic	-0.546	Destabilizing	0.999	D	0.63	neutral	None	None	None	None	N
P/D	0.6299	likely_pathogenic	0.6898	pathogenic	-0.236	Destabilizing	0.976	D	0.421	neutral	None	None	None	None	N
P/E	0.3531	ambiguous	0.3912	ambiguous	-0.358	Destabilizing	0.976	D	0.378	neutral	None	None	None	None	N
P/F	0.4942	ambiguous	0.579	pathogenic	-0.849	Destabilizing	0.996	D	0.64	neutral	None	None	None	None	N
P/G	0.3069	likely_benign	0.3492	ambiguous	-0.647	Destabilizing	0.851	D	0.451	neutral	None	None	None	None	N
P/H	0.2576	likely_benign	0.3145	benign	-0.244	Destabilizing	0.999	D	0.558	neutral	N	0.509738975	None	None	N
P/I	0.2881	likely_benign	0.3283	benign	-0.324	Destabilizing	0.988	D	0.634	neutral	None	None	None	None	N
P/K	0.4612	ambiguous	0.5272	ambiguous	-0.255	Destabilizing	0.976	D	0.399	neutral	None	None	None	None	N
P/L	0.1433	likely_benign	0.1722	benign	-0.324	Destabilizing	0.896	D	0.56	neutral	N	0.502079199	None	None	N
P/M	0.2847	likely_benign	0.3268	benign	-0.191	Destabilizing	0.999	D	0.561	neutral	None	None	None	None	N
P/N	0.3903	ambiguous	0.4357	ambiguous	0.026	Stabilizing	0.976	D	0.553	neutral	None	None	None	None	N
P/Q	0.1841	likely_benign	0.2136	benign	-0.272	Destabilizing	0.988	D	0.448	neutral	None	None	None	None	N
P/R	0.3233	likely_benign	0.3887	ambiguous	0.265	Stabilizing	0.968	D	0.569	neutral	N	0.518448707	None	None	N
P/S	0.1168	likely_benign	0.1338	benign	-0.376	Destabilizing	0.211	N	0.245	neutral	N	0.494811044	None	None	N
P/T	0.1056	likely_benign	0.1174	benign	-0.398	Destabilizing	0.811	D	0.429	neutral	N	0.513569706	None	None	N
P/V	0.1755	likely_benign	0.2051	benign	-0.353	Destabilizing	0.919	D	0.469	neutral	None	None	None	None	N
P/W	0.7207	likely_pathogenic	0.7883	pathogenic	-0.9	Destabilizing	0.999	D	0.628	neutral	None	None	None	None	N
P/Y	0.4922	ambiguous	0.5759	pathogenic	-0.568	Destabilizing	0.996	D	0.641	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.