TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20571	61936;61937;61938	chr2:178590014;178590013;178590012	chr2:179454741;179454740;179454739
N2AB	18930	57013;57014;57015	chr2:178590014;178590013;178590012	chr2:179454741;179454740;179454739
N2A	18003	54232;54233;54234	chr2:178590014;178590013;178590012	chr2:179454741;179454740;179454739
N2B	11506	34741;34742;34743	chr2:178590014;178590013;178590012	chr2:179454741;179454740;179454739
Novex-1	11631	35116;35117;35118	chr2:178590014;178590013;178590012	chr2:179454741;179454740;179454739
Novex-2	11698	35317;35318;35319	chr2:178590014;178590013;178590012	chr2:179454741;179454740;179454739
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGG
• RefSeq wild type template codon: CCC
• Domain: Fn3-37
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.1561
• 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
G/W	None	None	1.0	D	0.729	0.407	0.28798054836	gnomAD-4.0.0	6.8446E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99658E-07	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
G/A	0.5675	likely_pathogenic	0.5232	ambiguous	-0.829	Destabilizing	0.992	D	0.63	neutral	N	0.489446586	None	None	N
G/C	0.8922	likely_pathogenic	0.8876	pathogenic	-1.133	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
G/D	0.9581	likely_pathogenic	0.9556	pathogenic	-2.172	Highly Destabilizing	0.999	D	0.701	prob.neutral	None	None	None	None	N
G/E	0.9418	likely_pathogenic	0.9413	pathogenic	-2.234	Highly Destabilizing	0.999	D	0.754	deleterious	N	0.48333052	None	None	N
G/F	0.9773	likely_pathogenic	0.9753	pathogenic	-1.269	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
G/H	0.985	likely_pathogenic	0.9833	pathogenic	-1.376	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
G/I	0.9484	likely_pathogenic	0.9536	pathogenic	-0.501	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
G/K	0.98	likely_pathogenic	0.9788	pathogenic	-1.366	Destabilizing	0.999	D	0.755	deleterious	None	None	None	None	N
G/L	0.9333	likely_pathogenic	0.935	pathogenic	-0.501	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
G/M	0.9685	likely_pathogenic	0.9673	pathogenic	-0.366	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
G/N	0.9557	likely_pathogenic	0.9527	pathogenic	-1.173	Destabilizing	0.999	D	0.764	deleterious	None	None	None	None	N
G/P	0.9876	likely_pathogenic	0.9944	pathogenic	-0.573	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
G/Q	0.9596	likely_pathogenic	0.957	pathogenic	-1.437	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
G/R	0.9631	likely_pathogenic	0.9607	pathogenic	-0.981	Destabilizing	0.999	D	0.776	deleterious	N	0.518097453	None	None	N
G/S	0.5458	ambiguous	0.5053	ambiguous	-1.294	Destabilizing	0.927	D	0.473	neutral	None	None	None	None	N
G/T	0.8805	likely_pathogenic	0.888	pathogenic	-1.302	Destabilizing	0.998	D	0.707	prob.neutral	None	None	None	None	N
G/V	0.9126	likely_pathogenic	0.9235	pathogenic	-0.573	Destabilizing	0.999	D	0.775	deleterious	N	0.512363461	None	None	N
G/W	0.9793	likely_pathogenic	0.9786	pathogenic	-1.624	Destabilizing	1.0	D	0.729	prob.delet.	D	0.530721206	None	None	N
G/Y	0.9758	likely_pathogenic	0.9735	pathogenic	-1.231	Destabilizing	1.0	D	0.792	deleterious	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.