TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32445	97558;97559;97560	chr2:178542423;178542422;178542421	chr2:179407150;179407149;179407148
N2AB	30804	92635;92636;92637	chr2:178542423;178542422;178542421	chr2:179407150;179407149;179407148
N2A	29877	89854;89855;89856	chr2:178542423;178542422;178542421	chr2:179407150;179407149;179407148
N2B	23380	70363;70364;70365	chr2:178542423;178542422;178542421	chr2:179407150;179407149;179407148
Novex-1	23505	70738;70739;70740	chr2:178542423;178542422;178542421	chr2:179407150;179407149;179407148
Novex-2	23572	70939;70940;70941	chr2:178542423;178542422;178542421	chr2:179407150;179407149;179407148
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-124
• Domain position: 47
• Structural Position: 63
• Q(SASA): 0.7602
• 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
P/L	rs1330389316	-0.004	1.0	N	0.673	0.441	0.59105502098	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.59E-05	None	0	None	0	0	0
P/L	rs1330389316	-0.004	1.0	N	0.673	0.441	0.59105502098	gnomAD-4.0.0	1.59154E-06	None	None	None	None	N	None	0	0	None	0	2.77608E-05	None	0	0	0	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	0.2469	likely_benign	0.2206	benign	-0.34	Destabilizing	1.0	D	0.523	neutral	N	0.469591564	None	None	N
P/C	0.8869	likely_pathogenic	0.8565	pathogenic	-0.769	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
P/D	0.9041	likely_pathogenic	0.8854	pathogenic	-0.338	Destabilizing	1.0	D	0.557	neutral	None	None	None	None	N
P/E	0.7873	likely_pathogenic	0.7527	pathogenic	-0.457	Destabilizing	1.0	D	0.562	neutral	None	None	None	None	N
P/F	0.9158	likely_pathogenic	0.8867	pathogenic	-0.715	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
P/G	0.7269	likely_pathogenic	0.6986	pathogenic	-0.4	Destabilizing	1.0	D	0.634	neutral	None	None	None	None	N
P/H	0.7276	likely_pathogenic	0.6623	pathogenic	0.015	Stabilizing	1.0	D	0.654	neutral	None	None	None	None	N
P/I	0.7343	likely_pathogenic	0.6625	pathogenic	-0.326	Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	N
P/K	0.8423	likely_pathogenic	0.8087	pathogenic	-0.377	Destabilizing	1.0	D	0.558	neutral	None	None	None	None	N
P/L	0.4552	ambiguous	0.3758	ambiguous	-0.326	Destabilizing	1.0	D	0.673	neutral	N	0.470842357	None	None	N
P/M	0.7245	likely_pathogenic	0.6487	pathogenic	-0.569	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	N
P/N	0.8368	likely_pathogenic	0.7963	pathogenic	-0.16	Destabilizing	1.0	D	0.653	neutral	None	None	None	None	N
P/Q	0.6256	likely_pathogenic	0.5591	ambiguous	-0.382	Destabilizing	1.0	D	0.6	neutral	N	0.453467318	None	None	N
P/R	0.6967	likely_pathogenic	0.658	pathogenic	0.082	Stabilizing	1.0	D	0.651	neutral	N	0.474960098	None	None	N
P/S	0.5138	ambiguous	0.4644	ambiguous	-0.469	Destabilizing	1.0	D	0.576	neutral	N	0.418797384	None	None	N
P/T	0.4071	ambiguous	0.3555	ambiguous	-0.498	Destabilizing	1.0	D	0.567	neutral	N	0.372910379	None	None	N
P/V	0.5869	likely_pathogenic	0.507	ambiguous	-0.303	Destabilizing	1.0	D	0.628	neutral	None	None	None	None	N
P/W	0.9432	likely_pathogenic	0.9213	pathogenic	-0.766	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
P/Y	0.8914	likely_pathogenic	0.8543	pathogenic	-0.492	Destabilizing	1.0	D	0.694	prob.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.