TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8935	27028;27029;27030	chr2:178713331;178713330;178713329	chr2:179578058;179578057;179578056
N2AB	8618	26077;26078;26079	chr2:178713331;178713330;178713329	chr2:179578058;179578057;179578056
N2A	7691	23296;23297;23298	chr2:178713331;178713330;178713329	chr2:179578058;179578057;179578056
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: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-75
• Domain position: 10
• Structural Position: 13
• Q(SASA): 0.4217
• 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/R	rs571245328	-0.32	0.171	N	0.421	0.242	0.31411915649	gnomAD-2.1.1	1.93E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	4.57E-05	0
T/R	rs571245328	-0.32	0.171	N	0.421	0.242	0.31411915649	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	5.88E-05	0	0
T/R	rs571245328	-0.32	0.171	N	0.421	0.242	0.31411915649	gnomAD-4.0.0	9.59104E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.30161E-05	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	0.0736	likely_benign	0.0813	benign	-0.827	Destabilizing	None	N	0.073	neutral	N	0.489689982	None	None	N
T/C	0.3352	likely_benign	0.3567	ambiguous	-0.489	Destabilizing	0.001	N	0.23	neutral	None	None	None	None	N
T/D	0.3397	likely_benign	0.4459	ambiguous	-0.658	Destabilizing	0.072	N	0.418	neutral	None	None	None	None	N
T/E	0.2438	likely_benign	0.3164	benign	-0.648	Destabilizing	0.072	N	0.426	neutral	None	None	None	None	N
T/F	0.1698	likely_benign	0.2127	benign	-0.847	Destabilizing	0.214	N	0.413	neutral	None	None	None	None	N
T/G	0.2089	likely_benign	0.2354	benign	-1.106	Destabilizing	None	N	0.235	neutral	None	None	None	None	N
T/H	0.2397	likely_benign	0.2842	benign	-1.451	Destabilizing	0.864	D	0.373	neutral	None	None	None	None	N
T/I	0.0932	likely_benign	0.1153	benign	-0.169	Destabilizing	0.029	N	0.424	neutral	N	0.433777984	None	None	N
T/K	0.167	likely_benign	0.2108	benign	-0.909	Destabilizing	0.055	N	0.391	neutral	N	0.487036466	None	None	N
T/L	0.0894	likely_benign	0.1022	benign	-0.169	Destabilizing	0.006	N	0.358	neutral	None	None	None	None	N
T/M	0.0679	likely_benign	0.0733	benign	0.187	Stabilizing	0.007	N	0.305	neutral	None	None	None	None	N
T/N	0.1075	likely_benign	0.1368	benign	-0.873	Destabilizing	0.136	N	0.347	neutral	None	None	None	None	N
T/P	0.2733	likely_benign	0.3386	benign	-0.356	Destabilizing	0.171	N	0.424	neutral	D	0.530384598	None	None	N
T/Q	0.1884	likely_benign	0.2204	benign	-1.033	Destabilizing	0.356	N	0.406	neutral	None	None	None	None	N
T/R	0.1334	likely_benign	0.1633	benign	-0.677	Destabilizing	0.171	N	0.421	neutral	N	0.495829308	None	None	N
T/S	0.1051	likely_benign	0.1231	benign	-1.079	Destabilizing	0.012	N	0.334	neutral	N	0.517839376	None	None	N
T/V	0.0882	likely_benign	0.0967	benign	-0.356	Destabilizing	0.016	N	0.284	neutral	None	None	None	None	N
T/W	0.4328	ambiguous	0.4812	ambiguous	-0.814	Destabilizing	0.864	D	0.397	neutral	None	None	None	None	N
T/Y	0.2015	likely_benign	0.2329	benign	-0.584	Destabilizing	0.356	N	0.411	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.