TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28089	84490;84491;84492	chr2:178561867;178561866;178561865	chr2:179426594;179426593;179426592
N2AB	26448	79567;79568;79569	chr2:178561867;178561866;178561865	chr2:179426594;179426593;179426592
N2A	25521	76786;76787;76788	chr2:178561867;178561866;178561865	chr2:179426594;179426593;179426592
N2B	19024	57295;57296;57297	chr2:178561867;178561866;178561865	chr2:179426594;179426593;179426592
Novex-1	19149	57670;57671;57672	chr2:178561867;178561866;178561865	chr2:179426594;179426593;179426592
Novex-2	19216	57871;57872;57873	chr2:178561867;178561866;178561865	chr2:179426594;179426593;179426592
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: Fn3-92
• Domain position: 35
• Structural Position: 37
• Q(SASA): 0.1568
• 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	None	None	0.999	N	0.528	0.343	0.239305524855	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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	0.7297	likely_pathogenic	0.6863	pathogenic	-1.157	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
N/C	0.4715	ambiguous	0.3933	ambiguous	-0.457	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
N/D	0.7221	likely_pathogenic	0.6996	pathogenic	-1.422	Destabilizing	0.999	D	0.561	neutral	N	0.483877179	None	None	N
N/E	0.9617	likely_pathogenic	0.9543	pathogenic	-1.269	Destabilizing	0.999	D	0.64	neutral	None	None	None	None	N
N/F	0.9516	likely_pathogenic	0.9301	pathogenic	-0.857	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
N/G	0.4981	ambiguous	0.4606	ambiguous	-1.513	Destabilizing	0.999	D	0.526	neutral	None	None	None	None	N
N/H	0.2756	likely_benign	0.2306	benign	-1.055	Destabilizing	1.0	D	0.672	neutral	N	0.472520874	None	None	N
N/I	0.9289	likely_pathogenic	0.9104	pathogenic	-0.228	Destabilizing	1.0	D	0.887	deleterious	N	0.513364193	None	None	N
N/K	0.9076	likely_pathogenic	0.8835	pathogenic	-0.348	Destabilizing	1.0	D	0.665	neutral	N	0.469999205	None	None	N
N/L	0.8422	likely_pathogenic	0.813	pathogenic	-0.228	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
N/M	0.9145	likely_pathogenic	0.8948	pathogenic	0.186	Stabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
N/P	0.9856	likely_pathogenic	0.9848	pathogenic	-0.51	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
N/Q	0.8536	likely_pathogenic	0.8224	pathogenic	-1.135	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
N/R	0.8407	likely_pathogenic	0.8084	pathogenic	-0.31	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
N/S	0.1429	likely_benign	0.1306	benign	-1.213	Destabilizing	0.999	D	0.528	neutral	N	0.494948581	None	None	N
N/T	0.607	likely_pathogenic	0.5726	pathogenic	-0.869	Destabilizing	0.999	D	0.628	neutral	N	0.482636185	None	None	N
N/V	0.8981	likely_pathogenic	0.875	pathogenic	-0.51	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
N/W	0.9789	likely_pathogenic	0.9677	pathogenic	-0.6	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
N/Y	0.6089	likely_pathogenic	0.55	ambiguous	-0.341	Destabilizing	1.0	D	0.867	deleterious	N	0.473268115	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.