TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18430	55513;55514;55515	chr2:178601896;178601895;178601894	chr2:179466623;179466622;179466621
N2AB	16789	50590;50591;50592	chr2:178601896;178601895;178601894	chr2:179466623;179466622;179466621
N2A	15862	47809;47810;47811	chr2:178601896;178601895;178601894	chr2:179466623;179466622;179466621
N2B	9365	28318;28319;28320	chr2:178601896;178601895;178601894	chr2:179466623;179466622;179466621
Novex-1	9490	28693;28694;28695	chr2:178601896;178601895;178601894	chr2:179466623;179466622;179466621
Novex-2	9557	28894;28895;28896	chr2:178601896;178601895;178601894	chr2:179466623;179466622;179466621
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Ig-115
• Domain position: 49
• Structural Position: 69
• Q(SASA): 0.2249
• 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
P/S	rs970752412	-1.13	0.993	N	0.48	0.315	0.321672782286	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.96E-06	0
P/S	rs970752412	-1.13	0.993	N	0.48	0.315	0.321672782286	gnomAD-4.0.0	1.37005E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80001E-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
P/A	0.5206	ambiguous	0.5382	ambiguous	-2.449	Highly Destabilizing	0.98	D	0.464	neutral	N	0.488451034	None	None	N
P/C	0.9367	likely_pathogenic	0.9371	pathogenic	-2.033	Highly Destabilizing	1.0	D	0.663	neutral	None	None	None	None	N
P/D	0.9512	likely_pathogenic	0.9631	pathogenic	-3.54	Highly Destabilizing	0.999	D	0.531	neutral	None	None	None	None	N
P/E	0.9037	likely_pathogenic	0.9305	pathogenic	-3.269	Highly Destabilizing	0.999	D	0.512	neutral	None	None	None	None	N
P/F	0.9508	likely_pathogenic	0.9546	pathogenic	-1.484	Destabilizing	0.191	N	0.449	neutral	None	None	None	None	N
P/G	0.8805	likely_pathogenic	0.9004	pathogenic	-3.018	Highly Destabilizing	0.995	D	0.523	neutral	None	None	None	None	N
P/H	0.8475	likely_pathogenic	0.8872	pathogenic	-2.889	Highly Destabilizing	1.0	D	0.609	neutral	N	0.496555336	None	None	N
P/I	0.8492	likely_pathogenic	0.8353	pathogenic	-0.807	Destabilizing	0.942	D	0.542	neutral	None	None	None	None	N
P/K	0.9374	likely_pathogenic	0.956	pathogenic	-2.155	Highly Destabilizing	0.999	D	0.508	neutral	None	None	None	None	N
P/L	0.5359	ambiguous	0.5319	ambiguous	-0.807	Destabilizing	0.071	N	0.424	neutral	N	0.508076226	None	None	N
P/M	0.8432	likely_pathogenic	0.8488	pathogenic	-0.882	Destabilizing	0.991	D	0.611	neutral	None	None	None	None	N
P/N	0.9389	likely_pathogenic	0.9563	pathogenic	-2.685	Highly Destabilizing	0.999	D	0.605	neutral	None	None	None	None	N
P/Q	0.8448	likely_pathogenic	0.8922	pathogenic	-2.44	Highly Destabilizing	0.999	D	0.567	neutral	None	None	None	None	N
P/R	0.8862	likely_pathogenic	0.9145	pathogenic	-2.047	Highly Destabilizing	0.998	D	0.607	neutral	N	0.489211502	None	None	N
P/S	0.751	likely_pathogenic	0.8049	pathogenic	-3.217	Highly Destabilizing	0.993	D	0.48	neutral	N	0.515660288	None	None	N
P/T	0.6318	likely_pathogenic	0.6904	pathogenic	-2.803	Highly Destabilizing	0.98	D	0.473	neutral	D	0.525341351	None	None	N
P/V	0.744	likely_pathogenic	0.7248	pathogenic	-1.334	Destabilizing	0.942	D	0.513	neutral	None	None	None	None	N
P/W	0.9787	likely_pathogenic	0.9842	pathogenic	-2.136	Highly Destabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	N
P/Y	0.9645	likely_pathogenic	0.97	pathogenic	-1.793	Destabilizing	0.983	D	0.617	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.