TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15504	46735;46736;46737	chr2:178619807;178619806;178619805	chr2:179484534;179484533;179484532
N2AB	13863	41812;41813;41814	chr2:178619807;178619806;178619805	chr2:179484534;179484533;179484532
N2A	12936	39031;39032;39033	chr2:178619807;178619806;178619805	chr2:179484534;179484533;179484532
N2B	6439	19540;19541;19542	chr2:178619807;178619806;178619805	chr2:179484534;179484533;179484532
Novex-1	6564	19915;19916;19917	chr2:178619807;178619806;178619805	chr2:179484534;179484533;179484532
Novex-2	6631	20116;20117;20118	chr2:178619807;178619806;178619805	chr2:179484534;179484533;179484532
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-107
• Domain position: 25
• Structural Position: 38
• Q(SASA): 0.758
• 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
N/S	rs1184631064	0.004	0.904	N	0.398	0.361	0.193865811164	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	0	5.81E-05	None	0	0	None	0	None	0	0	0
N/S	rs1184631064	0.004	0.904	N	0.398	0.361	0.193865811164	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	6.57E-05	0	0	0	None	0	0	1.47E-05	0	0
N/S	rs1184631064	0.004	0.904	N	0.398	0.361	0.193865811164	gnomAD-4.0.0	6.82305E-06	None	None	None	None	N	None	1.33711E-05	6.68181E-05	None	0	0	None	0	0	5.08943E-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
N/A	0.8881	likely_pathogenic	0.9049	pathogenic	-0.542	Destabilizing	0.86	D	0.504	neutral	None	None	None	None	N
N/C	0.8692	likely_pathogenic	0.9017	pathogenic	0.14	Stabilizing	0.998	D	0.628	neutral	None	None	None	None	N
N/D	0.6112	likely_pathogenic	0.6973	pathogenic	0.112	Stabilizing	0.966	D	0.441	neutral	N	0.508993292	None	None	N
N/E	0.9597	likely_pathogenic	0.973	pathogenic	0.165	Stabilizing	0.993	D	0.512	neutral	None	None	None	None	N
N/F	0.9825	likely_pathogenic	0.9863	pathogenic	-0.491	Destabilizing	0.956	D	0.653	neutral	None	None	None	None	N
N/G	0.8513	likely_pathogenic	0.8719	pathogenic	-0.827	Destabilizing	0.926	D	0.401	neutral	None	None	None	None	N
N/H	0.7178	likely_pathogenic	0.7719	pathogenic	-0.578	Destabilizing	0.99	D	0.555	neutral	N	0.511093189	None	None	N
N/I	0.918	likely_pathogenic	0.93	pathogenic	0.153	Stabilizing	0.032	N	0.407	neutral	N	0.508993292	None	None	N
N/K	0.981	likely_pathogenic	0.9863	pathogenic	-0.035	Destabilizing	0.971	D	0.51	neutral	N	0.496054513	None	None	N
N/L	0.8988	likely_pathogenic	0.913	pathogenic	0.153	Stabilizing	0.514	D	0.517	neutral	None	None	None	None	N
N/M	0.9367	likely_pathogenic	0.9516	pathogenic	0.351	Stabilizing	0.988	D	0.597	neutral	None	None	None	None	N
N/P	0.969	likely_pathogenic	0.9601	pathogenic	-0.049	Destabilizing	0.993	D	0.606	neutral	None	None	None	None	N
N/Q	0.9363	likely_pathogenic	0.955	pathogenic	-0.526	Destabilizing	0.993	D	0.547	neutral	None	None	None	None	N
N/R	0.9703	likely_pathogenic	0.9763	pathogenic	-0.043	Destabilizing	0.993	D	0.56	neutral	None	None	None	None	N
N/S	0.184	likely_benign	0.2004	benign	-0.54	Destabilizing	0.904	D	0.398	neutral	N	0.393099612	None	None	N
N/T	0.5349	ambiguous	0.6055	pathogenic	-0.304	Destabilizing	0.822	D	0.464	neutral	N	0.472487212	None	None	N
N/V	0.9012	likely_pathogenic	0.9197	pathogenic	-0.049	Destabilizing	0.514	D	0.537	neutral	None	None	None	None	N
N/W	0.9909	likely_pathogenic	0.9936	pathogenic	-0.339	Destabilizing	0.998	D	0.676	prob.neutral	None	None	None	None	N
N/Y	0.8589	likely_pathogenic	0.8869	pathogenic	-0.106	Destabilizing	0.971	D	0.611	neutral	N	0.5112759	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.