TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21880	65863;65864;65865	chr2:178583165;178583164;178583163	chr2:179447892;179447891;179447890
N2AB	20239	60940;60941;60942	chr2:178583165;178583164;178583163	chr2:179447892;179447891;179447890
N2A	19312	58159;58160;58161	chr2:178583165;178583164;178583163	chr2:179447892;179447891;179447890
N2B	12815	38668;38669;38670	chr2:178583165;178583164;178583163	chr2:179447892;179447891;179447890
Novex-1	12940	39043;39044;39045	chr2:178583165;178583164;178583163	chr2:179447892;179447891;179447890
Novex-2	13007	39244;39245;39246	chr2:178583165;178583164;178583163	chr2:179447892;179447891;179447890
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-125
• Domain position: 15
• Structural Position: 26
• Q(SASA): 0.4961
• 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/K	None	None	0.014	N	0.272	0.059	0.0884992946249	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.21507E-04	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	0.3611	ambiguous	0.3076	benign	-0.69	Destabilizing	0.754	D	0.459	neutral	None	None	None	None	N
N/C	0.557	ambiguous	0.4758	ambiguous	0.196	Stabilizing	0.998	D	0.721	prob.delet.	None	None	None	None	N
N/D	0.2024	likely_benign	0.1817	benign	0.269	Stabilizing	0.822	D	0.399	neutral	N	0.412262909	None	None	N
N/E	0.7178	likely_pathogenic	0.6618	pathogenic	0.28	Stabilizing	0.754	D	0.38	neutral	None	None	None	None	N
N/F	0.8814	likely_pathogenic	0.8428	pathogenic	-0.869	Destabilizing	0.993	D	0.701	prob.neutral	None	None	None	None	N
N/G	0.4766	ambiguous	0.4147	ambiguous	-0.921	Destabilizing	0.86	D	0.379	neutral	None	None	None	None	N
N/H	0.226	likely_benign	0.1939	benign	-0.785	Destabilizing	0.97	D	0.485	neutral	N	0.482298997	None	None	N
N/I	0.5852	likely_pathogenic	0.5259	ambiguous	-0.148	Destabilizing	0.942	D	0.687	prob.neutral	N	0.498729887	None	None	N
N/K	0.6147	likely_pathogenic	0.5557	ambiguous	0.088	Stabilizing	0.014	N	0.272	neutral	N	0.444991403	None	None	N
N/L	0.5676	likely_pathogenic	0.5107	ambiguous	-0.148	Destabilizing	0.956	D	0.525	neutral	None	None	None	None	N
N/M	0.6224	likely_pathogenic	0.5709	pathogenic	0.264	Stabilizing	0.998	D	0.665	neutral	None	None	None	None	N
N/P	0.5928	likely_pathogenic	0.5391	ambiguous	-0.301	Destabilizing	0.978	D	0.653	neutral	None	None	None	None	N
N/Q	0.6222	likely_pathogenic	0.5635	ambiguous	-0.443	Destabilizing	0.956	D	0.465	neutral	None	None	None	None	N
N/R	0.6022	likely_pathogenic	0.5496	ambiguous	0.123	Stabilizing	0.754	D	0.406	neutral	None	None	None	None	N
N/S	0.1057	likely_benign	0.0977	benign	-0.38	Destabilizing	0.698	D	0.423	neutral	N	0.415167141	None	None	N
N/T	0.2123	likely_benign	0.1941	benign	-0.189	Destabilizing	0.058	N	0.246	neutral	N	0.397024097	None	None	N
N/V	0.4545	ambiguous	0.3994	ambiguous	-0.301	Destabilizing	0.956	D	0.556	neutral	None	None	None	None	N
N/W	0.9402	likely_pathogenic	0.9275	pathogenic	-0.714	Destabilizing	0.998	D	0.72	prob.delet.	None	None	None	None	N
N/Y	0.5025	ambiguous	0.4429	ambiguous	-0.49	Destabilizing	0.99	D	0.674	neutral	N	0.503751705	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.