TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22187	66784;66785;66786	chr2:178581709;178581708;178581707	chr2:179446436;179446435;179446434
N2AB	20546	61861;61862;61863	chr2:178581709;178581708;178581707	chr2:179446436;179446435;179446434
N2A	19619	59080;59081;59082	chr2:178581709;178581708;178581707	chr2:179446436;179446435;179446434
N2B	13122	39589;39590;39591	chr2:178581709;178581708;178581707	chr2:179446436;179446435;179446434
Novex-1	13247	39964;39965;39966	chr2:178581709;178581708;178581707	chr2:179446436;179446435;179446434
Novex-2	13314	40165;40166;40167	chr2:178581709;178581708;178581707	chr2:179446436;179446435;179446434
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: Fn3-49
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.6451
• Predicted PPI site: I

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/R	None	None	0.989	N	0.575	0.37	0.458464862945	gnomAD-4.0.0	6.85345E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.00336E-07	0	0
P/S	rs1160117316	None	0.961	N	0.478	0.36	0.357724736475	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
P/S	rs1160117316	None	0.961	N	0.478	0.36	0.357724736475	gnomAD-4.0.0	6.57644E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.47085E-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
P/A	0.1125	likely_benign	0.1127	benign	-0.667	Destabilizing	0.961	D	0.449	neutral	N	0.509016743	None	None	I
P/C	0.67	likely_pathogenic	0.7023	pathogenic	-0.625	Destabilizing	1.0	D	0.655	neutral	None	None	None	None	I
P/D	0.3766	ambiguous	0.3746	ambiguous	-0.305	Destabilizing	0.092	N	0.179	neutral	None	None	None	None	I
P/E	0.2343	likely_benign	0.2418	benign	-0.412	Destabilizing	0.155	N	0.159	neutral	None	None	None	None	I
P/F	0.7833	likely_pathogenic	0.7937	pathogenic	-0.814	Destabilizing	0.999	D	0.603	neutral	None	None	None	None	I
P/G	0.4403	ambiguous	0.465	ambiguous	-0.827	Destabilizing	0.985	D	0.519	neutral	None	None	None	None	I
P/H	0.3063	likely_benign	0.3257	benign	-0.368	Destabilizing	1.0	D	0.584	neutral	N	0.497314307	None	None	I
P/I	0.533	ambiguous	0.5505	ambiguous	-0.389	Destabilizing	0.999	D	0.619	neutral	None	None	None	None	I
P/K	0.3502	ambiguous	0.3804	ambiguous	-0.504	Destabilizing	0.97	D	0.467	neutral	None	None	None	None	I
P/L	0.2454	likely_benign	0.2571	benign	-0.389	Destabilizing	0.994	D	0.523	neutral	N	0.503999805	None	None	I
P/M	0.4744	ambiguous	0.4879	ambiguous	-0.325	Destabilizing	1.0	D	0.583	neutral	None	None	None	None	I
P/N	0.3578	ambiguous	0.3517	ambiguous	-0.213	Destabilizing	0.991	D	0.505	neutral	None	None	None	None	I
P/Q	0.188	likely_benign	0.2019	benign	-0.47	Destabilizing	0.991	D	0.468	neutral	None	None	None	None	I
P/R	0.2803	likely_benign	0.3152	benign	0.039	Stabilizing	0.989	D	0.575	neutral	N	0.481678814	None	None	I
P/S	0.1692	likely_benign	0.1724	benign	-0.628	Destabilizing	0.961	D	0.478	neutral	N	0.484690554	None	None	I
P/T	0.167	likely_benign	0.1722	benign	-0.63	Destabilizing	0.98	D	0.507	neutral	N	0.484121123	None	None	I
P/V	0.3322	likely_benign	0.3564	ambiguous	-0.445	Destabilizing	0.996	D	0.501	neutral	None	None	None	None	I
P/W	0.8542	likely_pathogenic	0.8745	pathogenic	-0.877	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	I
P/Y	0.6855	likely_pathogenic	0.705	pathogenic	-0.587	Destabilizing	0.999	D	0.608	neutral	None	None	None	None	I

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.