TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32413	97462;97463;97464	chr2:178542519;178542518;178542517	chr2:179407246;179407245;179407244
N2AB	30772	92539;92540;92541	chr2:178542519;178542518;178542517	chr2:179407246;179407245;179407244
N2A	29845	89758;89759;89760	chr2:178542519;178542518;178542517	chr2:179407246;179407245;179407244
N2B	23348	70267;70268;70269	chr2:178542519;178542518;178542517	chr2:179407246;179407245;179407244
Novex-1	23473	70642;70643;70644	chr2:178542519;178542518;178542517	chr2:179407246;179407245;179407244
Novex-2	23540	70843;70844;70845	chr2:178542519;178542518;178542517	chr2:179407246;179407245;179407244
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: Fn3-124
• Domain position: 15
• Structural Position: 16
• Q(SASA): 0.409
• 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/N	rs1695055645	None	0.822	N	0.471	0.255	0.139678290688	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	1.30924E-04	0	0	0	None	0	0	0	0	0
D/N	rs1695055645	None	0.822	N	0.471	0.255	0.139678290688	gnomAD-4.0.0	1.31453E-05	None	None	None	None	N	None	0	1.30924E-04	None	0	0	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
D/A	0.4586	ambiguous	0.3998	ambiguous	-0.266	Destabilizing	0.698	D	0.445	neutral	N	0.433888975	None	None	N
D/C	0.7692	likely_pathogenic	0.7166	pathogenic	0.063	Stabilizing	0.998	D	0.673	neutral	None	None	None	None	N
D/E	0.3717	ambiguous	0.3224	benign	-0.702	Destabilizing	0.014	N	0.229	neutral	N	0.435793129	None	None	N
D/F	0.8365	likely_pathogenic	0.7904	pathogenic	-0.628	Destabilizing	0.998	D	0.673	neutral	None	None	None	None	N
D/G	0.2797	likely_benign	0.26	benign	-0.52	Destabilizing	0.822	D	0.471	neutral	N	0.424805345	None	None	N
D/H	0.6123	likely_pathogenic	0.5421	ambiguous	-0.98	Destabilizing	0.992	D	0.533	neutral	N	0.443393892	None	None	N
D/I	0.7937	likely_pathogenic	0.7439	pathogenic	0.367	Stabilizing	0.978	D	0.689	prob.neutral	None	None	None	None	N
D/K	0.7999	likely_pathogenic	0.7624	pathogenic	0.007	Stabilizing	0.754	D	0.493	neutral	None	None	None	None	N
D/L	0.6783	likely_pathogenic	0.6255	pathogenic	0.367	Stabilizing	0.956	D	0.687	prob.neutral	None	None	None	None	N
D/M	0.8293	likely_pathogenic	0.7824	pathogenic	0.827	Stabilizing	0.998	D	0.655	neutral	None	None	None	None	N
D/N	0.144	likely_benign	0.13	benign	-0.25	Destabilizing	0.822	D	0.471	neutral	N	0.414820424	None	None	N
D/P	0.9743	likely_pathogenic	0.9693	pathogenic	0.18	Stabilizing	0.978	D	0.571	neutral	None	None	None	None	N
D/Q	0.7254	likely_pathogenic	0.6627	pathogenic	-0.197	Destabilizing	0.915	D	0.558	neutral	None	None	None	None	N
D/R	0.8267	likely_pathogenic	0.7787	pathogenic	-0.13	Destabilizing	0.956	D	0.625	neutral	None	None	None	None	N
D/S	0.1957	likely_benign	0.1746	benign	-0.431	Destabilizing	0.356	N	0.261	neutral	None	None	None	None	N
D/T	0.3214	likely_benign	0.2845	benign	-0.222	Destabilizing	0.754	D	0.492	neutral	None	None	None	None	N
D/V	0.6128	likely_pathogenic	0.5611	ambiguous	0.18	Stabilizing	0.942	D	0.687	prob.neutral	N	0.467713547	None	None	N
D/W	0.9727	likely_pathogenic	0.9653	pathogenic	-0.685	Destabilizing	0.998	D	0.662	neutral	None	None	None	None	N
D/Y	0.5771	likely_pathogenic	0.5216	ambiguous	-0.429	Destabilizing	0.997	D	0.669	neutral	N	0.460806217	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.