TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18495	55708;55709;55710	chr2:178601514;178601513;178601512	chr2:179466241;179466240;179466239
N2AB	16854	50785;50786;50787	chr2:178601514;178601513;178601512	chr2:179466241;179466240;179466239
N2A	15927	48004;48005;48006	chr2:178601514;178601513;178601512	chr2:179466241;179466240;179466239
N2B	9430	28513;28514;28515	chr2:178601514;178601513;178601512	chr2:179466241;179466240;179466239
Novex-1	9555	28888;28889;28890	chr2:178601514;178601513;178601512	chr2:179466241;179466240;179466239
Novex-2	9622	29089;29090;29091	chr2:178601514;178601513;178601512	chr2:179466241;179466240;179466239
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-22
• Domain position: 17
• Structural Position: 19
• Q(SASA): 0.2284
• 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
S/R	rs1213190093	-0.687	0.934	N	0.527	0.411	0.4897983601	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	1.14784E-04	0	None	0	0	None	0	None	0	0	0
S/R	rs1213190093	-0.687	0.934	N	0.527	0.411	0.4897983601	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
S/R	rs1213190093	-0.687	0.934	N	0.527	0.411	0.4897983601	gnomAD-4.0.0	6.84559E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.9985E-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
S/A	0.1675	likely_benign	0.1915	benign	-0.629	Destabilizing	0.525	D	0.348	neutral	None	None	None	None	N
S/C	0.1473	likely_benign	0.175	benign	-0.782	Destabilizing	0.997	D	0.507	neutral	N	0.479154962	None	None	N
S/D	0.8165	likely_pathogenic	0.8304	pathogenic	-1.365	Destabilizing	0.728	D	0.411	neutral	None	None	None	None	N
S/E	0.8233	likely_pathogenic	0.833	pathogenic	-1.338	Destabilizing	0.842	D	0.429	neutral	None	None	None	None	N
S/F	0.3135	likely_benign	0.3709	ambiguous	-0.932	Destabilizing	0.974	D	0.596	neutral	None	None	None	None	N
S/G	0.184	likely_benign	0.2167	benign	-0.87	Destabilizing	0.454	N	0.399	neutral	N	0.511081188	None	None	N
S/H	0.4632	ambiguous	0.5099	ambiguous	-1.443	Destabilizing	0.974	D	0.514	neutral	None	None	None	None	N
S/I	0.4801	ambiguous	0.5469	ambiguous	-0.09	Destabilizing	0.934	D	0.591	neutral	N	0.492232788	None	None	N
S/K	0.8723	likely_pathogenic	0.894	pathogenic	-0.808	Destabilizing	0.842	D	0.429	neutral	None	None	None	None	N
S/L	0.2217	likely_benign	0.2607	benign	-0.09	Destabilizing	0.728	D	0.533	neutral	None	None	None	None	N
S/M	0.2718	likely_benign	0.3507	ambiguous	0.193	Stabilizing	0.998	D	0.512	neutral	None	None	None	None	N
S/N	0.2678	likely_benign	0.3047	benign	-1.064	Destabilizing	0.012	N	0.177	neutral	N	0.516295006	None	None	N
S/P	0.9849	likely_pathogenic	0.984	pathogenic	-0.237	Destabilizing	0.974	D	0.533	neutral	None	None	None	None	N
S/Q	0.6424	likely_pathogenic	0.6941	pathogenic	-1.256	Destabilizing	0.974	D	0.46	neutral	None	None	None	None	N
S/R	0.834	likely_pathogenic	0.8528	pathogenic	-0.69	Destabilizing	0.934	D	0.527	neutral	N	0.484381975	None	None	N
S/T	0.0918	likely_benign	0.1062	benign	-0.896	Destabilizing	0.007	N	0.107	neutral	N	0.4501073	None	None	N
S/V	0.4168	ambiguous	0.486	ambiguous	-0.237	Destabilizing	0.728	D	0.523	neutral	None	None	None	None	N
S/W	0.6101	likely_pathogenic	0.6488	pathogenic	-1.013	Destabilizing	0.998	D	0.667	neutral	None	None	None	None	N
S/Y	0.3108	likely_benign	0.362	ambiguous	-0.662	Destabilizing	0.991	D	0.59	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.