TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9945	30058;30059;30060	chr2:178704639;178704638;178704637	chr2:179569366;179569365;179569364
N2AB	9628	29107;29108;29109	chr2:178704639;178704638;178704637	chr2:179569366;179569365;179569364
N2A	8701	26326;26327;26328	chr2:178704639;178704638;178704637	chr2:179569366;179569365;179569364
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-84
• Domain position: 46
• Structural Position: 111
• Q(SASA): 0.5662
• 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
D/G	rs763249086	0.068	0.062	None	0.347	0.109	0.152612264143	gnomAD-2.1.1	8.14E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.3E-05	None	0	9.01E-06	0
D/G	rs763249086	0.068	0.062	None	0.347	0.109	0.152612264143	gnomAD-4.0.0	2.05457E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80015E-06	1.1622E-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
D/A	0.1611	likely_benign	0.2048	benign	0.101	Stabilizing	0.002	N	0.316	neutral	None	None	None	None	N
D/C	0.6455	likely_pathogenic	0.7745	pathogenic	-0.045	Destabilizing	0.935	D	0.437	neutral	None	None	None	None	N
D/E	0.1289	likely_benign	0.1377	benign	-0.299	Destabilizing	0.027	N	0.361	neutral	None	None	None	None	N
D/F	0.7066	likely_pathogenic	0.8214	pathogenic	-0.052	Destabilizing	0.791	D	0.399	neutral	None	None	None	None	N
D/G	0.141	likely_benign	0.1949	benign	0.009	Stabilizing	0.062	N	0.347	neutral	None	None	None	None	N
D/H	0.2451	likely_benign	0.342	ambiguous	0.514	Stabilizing	0.317	N	0.305	neutral	None	None	None	None	N
D/I	0.4319	ambiguous	0.5793	pathogenic	0.272	Stabilizing	0.38	N	0.403	neutral	None	None	None	None	N
D/K	0.222	likely_benign	0.3031	benign	0.497	Stabilizing	0.001	N	0.259	neutral	None	None	None	None	N
D/L	0.41	ambiguous	0.5349	ambiguous	0.272	Stabilizing	0.38	N	0.397	neutral	None	None	None	None	N
D/M	0.6425	likely_pathogenic	0.7578	pathogenic	0.099	Stabilizing	0.935	D	0.403	neutral	None	None	None	None	N
D/N	0.0848	likely_benign	0.1033	benign	0.312	Stabilizing	None	N	0.227	neutral	None	None	None	None	N
D/P	0.4299	ambiguous	0.4892	ambiguous	0.234	Stabilizing	0.001	N	0.262	neutral	None	None	None	None	N
D/Q	0.2559	likely_benign	0.3396	benign	0.306	Stabilizing	0.235	N	0.317	neutral	None	None	None	None	N
D/R	0.2808	likely_benign	0.4063	ambiguous	0.655	Stabilizing	0.235	N	0.36	neutral	None	None	None	None	N
D/S	0.0974	likely_benign	0.1239	benign	0.221	Stabilizing	0.081	N	0.345	neutral	None	None	None	None	N
D/T	0.2418	likely_benign	0.3166	benign	0.3	Stabilizing	0.081	N	0.335	neutral	None	None	None	None	N
D/V	0.2733	likely_benign	0.375	ambiguous	0.234	Stabilizing	0.317	N	0.391	neutral	None	None	None	None	N
D/W	0.8821	likely_pathogenic	0.9362	pathogenic	-0.047	Destabilizing	0.935	D	0.528	neutral	None	None	None	None	N
D/Y	0.3316	likely_benign	0.4545	ambiguous	0.165	Stabilizing	0.741	D	0.398	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.