TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33208	99847;99848;99849	chr2:178537585;178537584;178537583	chr2:179402312;179402311;179402310
N2AB	31567	94924;94925;94926	chr2:178537585;178537584;178537583	chr2:179402312;179402311;179402310
N2A	30640	92143;92144;92145	chr2:178537585;178537584;178537583	chr2:179402312;179402311;179402310
N2B	24143	72652;72653;72654	chr2:178537585;178537584;178537583	chr2:179402312;179402311;179402310
Novex-1	24268	73027;73028;73029	chr2:178537585;178537584;178537583	chr2:179402312;179402311;179402310
Novex-2	24335	73228;73229;73230	chr2:178537585;178537584;178537583	chr2:179402312;179402311;179402310
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-157
• Domain position: 6
• Structural Position: 16
• Q(SASA): 0.213
• 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
G/R	None	None	0.922	N	0.581	0.371	0.52540932818	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
G/A	0.0771	likely_benign	0.1029	benign	-0.551	Destabilizing	None	N	0.289	neutral	N	0.353963967	None	None	N
G/C	0.2336	likely_benign	0.2986	benign	-0.839	Destabilizing	0.978	D	0.589	neutral	None	None	None	None	N
G/D	0.7506	likely_pathogenic	0.7664	pathogenic	-0.674	Destabilizing	0.922	D	0.597	neutral	None	None	None	None	N
G/E	0.6946	likely_pathogenic	0.702	pathogenic	-0.731	Destabilizing	0.922	D	0.576	neutral	N	0.408993317	None	None	N
G/F	0.8253	likely_pathogenic	0.8462	pathogenic	-0.845	Destabilizing	0.969	D	0.61	neutral	None	None	None	None	N
G/H	0.7943	likely_pathogenic	0.8145	pathogenic	-1.132	Destabilizing	0.997	D	0.569	neutral	None	None	None	None	N
G/I	0.4116	ambiguous	0.4869	ambiguous	-0.176	Destabilizing	0.056	N	0.5	neutral	None	None	None	None	N
G/K	0.8488	likely_pathogenic	0.8435	pathogenic	-1.056	Destabilizing	0.94	D	0.583	neutral	None	None	None	None	N
G/L	0.6019	likely_pathogenic	0.6634	pathogenic	-0.176	Destabilizing	0.48	N	0.585	neutral	None	None	None	None	N
G/M	0.6449	likely_pathogenic	0.695	pathogenic	-0.243	Destabilizing	0.969	D	0.596	neutral	None	None	None	None	N
G/N	0.7257	likely_pathogenic	0.7573	pathogenic	-0.731	Destabilizing	0.969	D	0.641	neutral	None	None	None	None	N
G/P	0.9586	likely_pathogenic	0.9595	pathogenic	-0.259	Destabilizing	0.922	D	0.579	neutral	None	None	None	None	N
G/Q	0.7297	likely_pathogenic	0.75	pathogenic	-0.877	Destabilizing	0.969	D	0.603	neutral	None	None	None	None	N
G/R	0.7102	likely_pathogenic	0.7323	pathogenic	-0.808	Destabilizing	0.922	D	0.581	neutral	N	0.390234198	None	None	N
G/S	0.1474	likely_benign	0.1863	benign	-1.041	Destabilizing	0.281	N	0.604	neutral	None	None	None	None	N
G/T	0.2045	likely_benign	0.2478	benign	-1.007	Destabilizing	0.817	D	0.559	neutral	None	None	None	None	N
G/V	0.2385	likely_benign	0.3099	benign	-0.259	Destabilizing	0.41	N	0.598	neutral	N	0.313554565	None	None	N
G/W	0.8318	likely_pathogenic	0.8485	pathogenic	-1.201	Destabilizing	0.997	D	0.597	neutral	None	None	None	None	N
G/Y	0.7906	likely_pathogenic	0.8243	pathogenic	-0.763	Destabilizing	0.99	D	0.603	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.