TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5564	16915;16916;16917	chr2:178732279;178732278;178732277	chr2:179597006;179597005;179597004
N2AB	5247	15964;15965;15966	chr2:178732279;178732278;178732277	chr2:179597006;179597005;179597004
N2A	4320	13183;13184;13185	chr2:178732279;178732278;178732277	chr2:179597006;179597005;179597004
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: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-39
• Domain position: 22
• Structural Position: 31
• Q(SASA): 0.3316
• 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
A/G	rs1251516038	-1.215	0.024	N	0.314	0.069	0.298403945805	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	9.43E-05	0	0	0	0
A/G	rs1251516038	-1.215	0.024	N	0.314	0.069	0.298403945805	gnomAD-4.0.0	6.57428E-06	None	None	None	None	N	None	0	0	None	0	0	None	9.42507E-05	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
A/C	0.3521	ambiguous	0.3835	ambiguous	-0.84	Destabilizing	0.676	D	0.446	neutral	None	None	None	None	N
A/D	0.1693	likely_benign	0.1693	benign	-1.621	Destabilizing	None	N	0.369	neutral	N	0.418907319	None	None	N
A/E	0.1404	likely_benign	0.1334	benign	-1.615	Destabilizing	None	N	0.267	neutral	None	None	None	None	N
A/F	0.1796	likely_benign	0.183	benign	-1.063	Destabilizing	0.214	N	0.523	neutral	None	None	None	None	N
A/G	0.1244	likely_benign	0.1275	benign	-1.333	Destabilizing	0.024	N	0.314	neutral	N	0.465738474	None	None	N
A/H	0.2576	likely_benign	0.2655	benign	-1.63	Destabilizing	0.356	N	0.501	neutral	None	None	None	None	N
A/I	0.124	likely_benign	0.1243	benign	-0.333	Destabilizing	0.013	N	0.44	neutral	None	None	None	None	N
A/K	0.2419	likely_benign	0.2372	benign	-1.312	Destabilizing	0.016	N	0.405	neutral	None	None	None	None	N
A/L	0.1052	likely_benign	0.107	benign	-0.333	Destabilizing	0.016	N	0.383	neutral	None	None	None	None	N
A/M	0.1526	likely_benign	0.1559	benign	-0.201	Destabilizing	0.214	N	0.468	neutral	None	None	None	None	N
A/N	0.1522	likely_benign	0.1506	benign	-1.067	Destabilizing	0.072	N	0.479	neutral	None	None	None	None	N
A/P	0.3197	likely_benign	0.3111	benign	-0.523	Destabilizing	0.106	N	0.445	neutral	N	0.421659623	None	None	N
A/Q	0.1947	likely_benign	0.196	benign	-1.187	Destabilizing	0.038	N	0.429	neutral	None	None	None	None	N
A/R	0.2096	likely_benign	0.2028	benign	-1.007	Destabilizing	0.072	N	0.471	neutral	None	None	None	None	N
A/S	0.0774	likely_benign	0.0768	benign	-1.392	Destabilizing	0.012	N	0.347	neutral	N	0.417675168	None	None	N
A/T	0.0711	likely_benign	0.0692	benign	-1.294	Destabilizing	None	N	0.185	neutral	N	0.404225868	None	None	N
A/V	0.0831	likely_benign	0.0834	benign	-0.523	Destabilizing	None	N	0.194	neutral	N	0.435031565	None	None	N
A/W	0.4864	ambiguous	0.5059	ambiguous	-1.521	Destabilizing	0.864	D	0.557	neutral	None	None	None	None	N
A/Y	0.2614	likely_benign	0.2734	benign	-1.087	Destabilizing	0.356	N	0.514	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.