TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33258	99997;99998;99999	chr2:178537435;178537434;178537433	chr2:179402162;179402161;179402160
N2AB	31617	95074;95075;95076	chr2:178537435;178537434;178537433	chr2:179402162;179402161;179402160
N2A	30690	92293;92294;92295	chr2:178537435;178537434;178537433	chr2:179402162;179402161;179402160
N2B	24193	72802;72803;72804	chr2:178537435;178537434;178537433	chr2:179402162;179402161;179402160
Novex-1	24318	73177;73178;73179	chr2:178537435;178537434;178537433	chr2:179402162;179402161;179402160
Novex-2	24385	73378;73379;73380	chr2:178537435;178537434;178537433	chr2:179402162;179402161;179402160
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-157
• Domain position: 56
• Structural Position: 143
• Q(SASA): 0.459
• 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/H	None	None	0.999	N	0.609	0.369	0.270889551736	gnomAD-4.0.0	2.40065E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62501E-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	0.5	ambiguous	0.5317	ambiguous	-0.479	Destabilizing	0.619	D	0.545	neutral	None	None	None	None	N
N/C	0.6539	likely_pathogenic	0.7258	pathogenic	0.416	Stabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
N/D	0.1619	likely_benign	0.1678	benign	-0.344	Destabilizing	0.939	D	0.495	neutral	N	0.485261944	None	None	N
N/E	0.5287	ambiguous	0.5466	ambiguous	-0.34	Destabilizing	0.996	D	0.552	neutral	None	None	None	None	N
N/F	0.7915	likely_pathogenic	0.8286	pathogenic	-0.63	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
N/G	0.4682	ambiguous	0.4878	ambiguous	-0.723	Destabilizing	0.208	N	0.258	neutral	None	None	None	None	N
N/H	0.2083	likely_benign	0.2237	benign	-0.755	Destabilizing	0.999	D	0.609	neutral	N	0.479840438	None	None	N
N/I	0.6279	likely_pathogenic	0.6948	pathogenic	0.097	Stabilizing	0.999	D	0.742	deleterious	N	0.480854396	None	None	N
N/K	0.465	ambiguous	0.4845	ambiguous	-0.067	Destabilizing	0.999	D	0.569	neutral	N	0.485955378	None	None	N
N/L	0.5872	likely_pathogenic	0.6385	pathogenic	0.097	Stabilizing	0.997	D	0.718	prob.delet.	None	None	None	None	N
N/M	0.5848	likely_pathogenic	0.6342	pathogenic	0.684	Stabilizing	1.0	D	0.664	neutral	None	None	None	None	N
N/P	0.953	likely_pathogenic	0.9651	pathogenic	-0.066	Destabilizing	0.995	D	0.681	prob.neutral	None	None	None	None	N
N/Q	0.5074	ambiguous	0.5175	ambiguous	-0.582	Destabilizing	0.999	D	0.609	neutral	None	None	None	None	N
N/R	0.5829	likely_pathogenic	0.6076	pathogenic	0.002	Stabilizing	0.999	D	0.621	neutral	None	None	None	None	N
N/S	0.1997	likely_benign	0.212	benign	-0.351	Destabilizing	0.884	D	0.419	neutral	N	0.50679201	None	None	N
N/T	0.3196	likely_benign	0.3569	ambiguous	-0.192	Destabilizing	0.96	D	0.557	neutral	N	0.479840438	None	None	N
N/V	0.615	likely_pathogenic	0.6723	pathogenic	-0.066	Destabilizing	0.965	D	0.725	prob.delet.	None	None	None	None	N
N/W	0.9238	likely_pathogenic	0.9369	pathogenic	-0.527	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
N/Y	0.2701	likely_benign	0.3133	benign	-0.294	Destabilizing	1.0	D	0.683	prob.neutral	N	0.462243162	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.