TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31767	95524;95525;95526	chr2:178545937;178545936;178545935	chr2:179410664;179410663;179410662
N2AB	30126	90601;90602;90603	chr2:178545937;178545936;178545935	chr2:179410664;179410663;179410662
N2A	29199	87820;87821;87822	chr2:178545937;178545936;178545935	chr2:179410664;179410663;179410662
N2B	22702	68329;68330;68331	chr2:178545937;178545936;178545935	chr2:179410664;179410663;179410662
Novex-1	22827	68704;68705;68706	chr2:178545937;178545936;178545935	chr2:179410664;179410663;179410662
Novex-2	22894	68905;68906;68907	chr2:178545937;178545936;178545935	chr2:179410664;179410663;179410662
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-119
• Domain position: 60
• Structural Position: 91
• Q(SASA): 0.1921
• Predicted PPI site: I

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
Y/C	rs1431446089	-1.294	None	N	0.396	0.233	0.345859378078	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
Y/C	rs1431446089	-1.294	None	N	0.396	0.233	0.345859378078	gnomAD-4.0.0	4.77354E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.57456E-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
Y/A	0.1804	likely_benign	0.1886	benign	-2.269	Highly Destabilizing	0.007	N	0.442	neutral	None	None	None	None	I
Y/C	0.0456	likely_benign	0.0545	benign	-1.257	Destabilizing	None	N	0.396	neutral	N	0.434175055	None	None	I
Y/D	0.4287	ambiguous	0.3606	ambiguous	-1.366	Destabilizing	0.055	N	0.513	neutral	N	0.518269399	None	None	I
Y/E	0.53	ambiguous	0.4572	ambiguous	-1.238	Destabilizing	0.038	N	0.526	neutral	None	None	None	None	I
Y/F	0.0741	likely_benign	0.0779	benign	-0.781	Destabilizing	0.055	N	0.385	neutral	N	0.423456629	None	None	I
Y/G	0.2336	likely_benign	0.2715	benign	-2.624	Highly Destabilizing	0.031	N	0.475	neutral	None	None	None	None	I
Y/H	0.0929	likely_benign	0.0833	benign	-1.062	Destabilizing	None	N	0.187	neutral	N	0.475117601	None	None	I
Y/I	0.2382	likely_benign	0.2229	benign	-1.17	Destabilizing	0.072	N	0.469	neutral	None	None	None	None	I
Y/K	0.3942	ambiguous	0.3775	ambiguous	-1.592	Destabilizing	0.072	N	0.529	neutral	None	None	None	None	I
Y/L	0.217	likely_benign	0.2109	benign	-1.17	Destabilizing	0.016	N	0.427	neutral	None	None	None	None	I
Y/M	0.3171	likely_benign	0.322	benign	-0.948	Destabilizing	0.628	D	0.509	neutral	None	None	None	None	I
Y/N	0.1697	likely_benign	0.1455	benign	-2.131	Highly Destabilizing	0.029	N	0.516	neutral	N	0.506659604	None	None	I
Y/P	0.9005	likely_pathogenic	0.8804	pathogenic	-1.536	Destabilizing	0.136	N	0.611	neutral	None	None	None	None	I
Y/Q	0.2834	likely_benign	0.2524	benign	-1.935	Destabilizing	0.214	N	0.557	neutral	None	None	None	None	I
Y/R	0.2459	likely_benign	0.2399	benign	-1.281	Destabilizing	0.072	N	0.539	neutral	None	None	None	None	I
Y/S	0.1265	likely_benign	0.1276	benign	-2.591	Highly Destabilizing	0.012	N	0.431	neutral	N	0.521698039	None	None	I
Y/T	0.1761	likely_benign	0.1729	benign	-2.357	Highly Destabilizing	None	N	0.409	neutral	None	None	None	None	I
Y/V	0.1594	likely_benign	0.1641	benign	-1.536	Destabilizing	0.016	N	0.385	neutral	None	None	None	None	I
Y/W	0.2856	likely_benign	0.3104	benign	-0.345	Destabilizing	0.628	D	0.479	neutral	None	None	None	None	I

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.