TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35758	107497;107498;107499	chr2:178528379;178528378;178528377	chr2:179393106;179393105;179393104
N2AB	34117	102574;102575;102576	chr2:178528379;178528378;178528377	chr2:179393106;179393105;179393104
N2A	33190	99793;99794;99795	chr2:178528379;178528378;178528377	chr2:179393106;179393105;179393104
N2B	26693	80302;80303;80304	chr2:178528379;178528378;178528377	chr2:179393106;179393105;179393104
Novex-1	26818	80677;80678;80679	chr2:178528379;178528378;178528377	chr2:179393106;179393105;179393104
Novex-2	26885	80878;80879;80880	chr2:178528379;178528378;178528377	chr2:179393106;179393105;179393104
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Ig-168
• Domain position: 57
• Structural Position: 137
• Q(SASA): 0.1531
• 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/C	rs1318791339	-0.435	0.78	N	0.617	0.403	0.567569374525	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
S/C	rs1318791339	-0.435	0.78	N	0.617	0.403	0.567569374525	gnomAD-4.0.0	6.36402E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	5.73099E-05	0
S/F	None	None	0.484	N	0.663	0.345	0.703042832254	gnomAD-4.0.0	1.591E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8577E-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
S/A	0.0991	likely_benign	0.0986	benign	-0.786	Destabilizing	0.027	N	0.497	neutral	N	0.487164495	None	None	N
S/C	0.1524	likely_benign	0.1501	benign	-0.42	Destabilizing	0.78	D	0.617	neutral	N	0.514284878	None	None	N
S/D	0.5605	ambiguous	0.545	ambiguous	-0.636	Destabilizing	0.001	N	0.317	neutral	None	None	None	None	N
S/E	0.6002	likely_pathogenic	0.5808	pathogenic	-0.472	Destabilizing	0.081	N	0.6	neutral	None	None	None	None	N
S/F	0.227	likely_benign	0.212	benign	-0.742	Destabilizing	0.484	N	0.663	neutral	N	0.49723058	None	None	N
S/G	0.146	likely_benign	0.1436	benign	-1.175	Destabilizing	0.067	N	0.583	neutral	None	None	None	None	N
S/H	0.318	likely_benign	0.3009	benign	-1.512	Destabilizing	0.935	D	0.625	neutral	None	None	None	None	N
S/I	0.1753	likely_benign	0.1678	benign	0.192	Stabilizing	0.235	N	0.668	neutral	None	None	None	None	N
S/K	0.6488	likely_pathogenic	0.6206	pathogenic	-0.057	Destabilizing	0.149	N	0.623	neutral	None	None	None	None	N
S/L	0.122	likely_benign	0.123	benign	0.192	Stabilizing	0.081	N	0.643	neutral	None	None	None	None	N
S/M	0.2097	likely_benign	0.2185	benign	0.189	Stabilizing	0.824	D	0.625	neutral	None	None	None	None	N
S/N	0.1723	likely_benign	0.1619	benign	-0.606	Destabilizing	0.149	N	0.604	neutral	None	None	None	None	N
S/P	0.9343	likely_pathogenic	0.9253	pathogenic	-0.098	Destabilizing	0.484	N	0.676	prob.neutral	D	0.525387694	None	None	N
S/Q	0.4792	ambiguous	0.4687	ambiguous	-0.416	Destabilizing	0.555	D	0.659	neutral	None	None	None	None	N
S/R	0.5268	ambiguous	0.4892	ambiguous	-0.415	Destabilizing	0.38	N	0.668	neutral	None	None	None	None	N
S/T	0.0674	likely_benign	0.0705	benign	-0.41	Destabilizing	None	N	0.241	neutral	N	0.475643249	None	None	N
S/V	0.1941	likely_benign	0.1902	benign	-0.098	Destabilizing	0.081	N	0.643	neutral	None	None	None	None	N
S/W	0.4171	ambiguous	0.4044	ambiguous	-0.878	Destabilizing	0.935	D	0.712	prob.delet.	None	None	None	None	N
S/Y	0.2015	likely_benign	0.1891	benign	-0.457	Destabilizing	0.484	N	0.64	neutral	N	0.502510499	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.