TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35721	107386;107387;107388	chr2:178528590;178528589;178528588	chr2:179393317;179393316;179393315
N2AB	34080	102463;102464;102465	chr2:178528590;178528589;178528588	chr2:179393317;179393316;179393315
N2A	33153	99682;99683;99684	chr2:178528590;178528589;178528588	chr2:179393317;179393316;179393315
N2B	26656	80191;80192;80193	chr2:178528590;178528589;178528588	chr2:179393317;179393316;179393315
Novex-1	26781	80566;80567;80568	chr2:178528590;178528589;178528588	chr2:179393317;179393316;179393315
Novex-2	26848	80767;80768;80769	chr2:178528590;178528589;178528588	chr2:179393317;179393316;179393315
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-168
• Domain position: 20
• Structural Position: 30
• Q(SASA): 0.0806
• 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
F/S	None	None	0.971	D	0.845	0.853	0.88957548057	gnomAD-4.0.0	1.59292E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86051E-06	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
F/A	0.9928	likely_pathogenic	0.9939	pathogenic	-2.367	Highly Destabilizing	0.86	D	0.803	deleterious	None	None	None	None	N
F/C	0.9687	likely_pathogenic	0.9757	pathogenic	-1.371	Destabilizing	0.997	D	0.853	deleterious	D	0.620307803	None	None	N
F/D	0.9991	likely_pathogenic	0.9993	pathogenic	-3.227	Highly Destabilizing	0.993	D	0.88	deleterious	None	None	None	None	N
F/E	0.9988	likely_pathogenic	0.999	pathogenic	-2.967	Highly Destabilizing	0.978	D	0.886	deleterious	None	None	None	None	N
F/G	0.9969	likely_pathogenic	0.9973	pathogenic	-2.852	Highly Destabilizing	0.978	D	0.875	deleterious	None	None	None	None	N
F/H	0.9901	likely_pathogenic	0.9898	pathogenic	-2.003	Highly Destabilizing	0.998	D	0.753	deleterious	None	None	None	None	N
F/I	0.7797	likely_pathogenic	0.8212	pathogenic	-0.769	Destabilizing	0.698	D	0.679	prob.neutral	N	0.521101472	None	None	N
F/K	0.9988	likely_pathogenic	0.9989	pathogenic	-1.922	Destabilizing	0.978	D	0.884	deleterious	None	None	None	None	N
F/L	0.9299	likely_pathogenic	0.8811	pathogenic	-0.769	Destabilizing	0.014	N	0.319	neutral	N	0.482609294	None	None	N
F/M	0.9054	likely_pathogenic	0.9181	pathogenic	-0.605	Destabilizing	0.956	D	0.663	neutral	None	None	None	None	N
F/N	0.9973	likely_pathogenic	0.9976	pathogenic	-2.637	Highly Destabilizing	0.993	D	0.88	deleterious	None	None	None	None	N
F/P	0.9998	likely_pathogenic	0.9998	pathogenic	-1.318	Destabilizing	0.993	D	0.885	deleterious	None	None	None	None	N
F/Q	0.9971	likely_pathogenic	0.9974	pathogenic	-2.377	Highly Destabilizing	0.993	D	0.884	deleterious	None	None	None	None	N
F/R	0.9963	likely_pathogenic	0.997	pathogenic	-1.916	Destabilizing	0.978	D	0.882	deleterious	None	None	None	None	N
F/S	0.9941	likely_pathogenic	0.9945	pathogenic	-3.093	Highly Destabilizing	0.971	D	0.845	deleterious	D	0.620307803	None	None	N
F/T	0.9958	likely_pathogenic	0.9962	pathogenic	-2.699	Highly Destabilizing	0.956	D	0.835	deleterious	None	None	None	None	N
F/V	0.8601	likely_pathogenic	0.8903	pathogenic	-1.318	Destabilizing	0.698	D	0.734	prob.delet.	N	0.511840386	None	None	N
F/W	0.9214	likely_pathogenic	0.9217	pathogenic	-0.175	Destabilizing	0.998	D	0.661	neutral	None	None	None	None	N
F/Y	0.6724	likely_pathogenic	0.6675	pathogenic	-0.586	Destabilizing	0.904	D	0.613	neutral	D	0.578548526	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.