TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31375	94348;94349;94350	chr2:178547503;178547502;178547501	chr2:179412230;179412229;179412228
N2AB	29734	89425;89426;89427	chr2:178547503;178547502;178547501	chr2:179412230;179412229;179412228
N2A	28807	86644;86645;86646	chr2:178547503;178547502;178547501	chr2:179412230;179412229;179412228
N2B	22310	67153;67154;67155	chr2:178547503;178547502;178547501	chr2:179412230;179412229;179412228
Novex-1	22435	67528;67529;67530	chr2:178547503;178547502;178547501	chr2:179412230;179412229;179412228
Novex-2	22502	67729;67730;67731	chr2:178547503;178547502;178547501	chr2:179412230;179412229;179412228
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-116
• Domain position: 68
• Structural Position: 99
• Q(SASA): 0.3137
• 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
K/N	None	None	1.0	N	0.659	0.293	0.235664433957	gnomAD-4.0.0	3.18424E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.86689E-05	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
K/A	0.6452	likely_pathogenic	0.7174	pathogenic	-0.549	Destabilizing	0.999	D	0.64	neutral	None	None	None	None	N
K/C	0.8972	likely_pathogenic	0.9166	pathogenic	-0.491	Destabilizing	1.0	D	0.651	neutral	None	None	None	None	N
K/D	0.8661	likely_pathogenic	0.894	pathogenic	-0.17	Destabilizing	1.0	D	0.642	neutral	None	None	None	None	N
K/E	0.4422	ambiguous	0.5584	ambiguous	-0.06	Destabilizing	0.999	D	0.653	neutral	N	0.409580468	None	None	N
K/F	0.9833	likely_pathogenic	0.9898	pathogenic	-0.217	Destabilizing	1.0	D	0.631	neutral	None	None	None	None	N
K/G	0.7625	likely_pathogenic	0.8081	pathogenic	-0.912	Destabilizing	1.0	D	0.601	neutral	None	None	None	None	N
K/H	0.6459	likely_pathogenic	0.6875	pathogenic	-1.238	Destabilizing	1.0	D	0.605	neutral	None	None	None	None	N
K/I	0.8612	likely_pathogenic	0.9024	pathogenic	0.388	Stabilizing	1.0	D	0.634	neutral	N	0.489774835	None	None	N
K/L	0.81	likely_pathogenic	0.8522	pathogenic	0.388	Stabilizing	1.0	D	0.601	neutral	None	None	None	None	N
K/M	0.6667	likely_pathogenic	0.7607	pathogenic	0.193	Stabilizing	1.0	D	0.601	neutral	None	None	None	None	N
K/N	0.7849	likely_pathogenic	0.8227	pathogenic	-0.449	Destabilizing	1.0	D	0.659	neutral	N	0.479019123	None	None	N
K/P	0.6468	likely_pathogenic	0.6802	pathogenic	0.106	Stabilizing	1.0	D	0.613	neutral	None	None	None	None	N
K/Q	0.2727	likely_benign	0.3343	benign	-0.478	Destabilizing	1.0	D	0.667	neutral	N	0.470668999	None	None	N
K/R	0.0984	likely_benign	0.1003	benign	-0.625	Destabilizing	0.999	D	0.651	neutral	N	0.487542606	None	None	N
K/S	0.7392	likely_pathogenic	0.7868	pathogenic	-1.039	Destabilizing	0.999	D	0.658	neutral	None	None	None	None	N
K/T	0.4707	ambiguous	0.5483	ambiguous	-0.723	Destabilizing	1.0	D	0.634	neutral	N	0.454968828	None	None	N
K/V	0.7765	likely_pathogenic	0.8281	pathogenic	0.106	Stabilizing	1.0	D	0.607	neutral	None	None	None	None	N
K/W	0.9661	likely_pathogenic	0.9742	pathogenic	-0.126	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	N
K/Y	0.9313	likely_pathogenic	0.9504	pathogenic	0.144	Stabilizing	1.0	D	0.603	neutral	None	None	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.