TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9241	27946;27947;27948	chr2:178712109;178712108;178712107	chr2:179576836;179576835;179576834
N2AB	8924	26995;26996;26997	chr2:178712109;178712108;178712107	chr2:179576836;179576835;179576834
N2A	7997	24214;24215;24216	chr2:178712109;178712108;178712107	chr2:179576836;179576835;179576834
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-78
• Domain position: 37
• Structural Position: 51
• Q(SASA): 0.3125
• 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/E	rs2154295843	None	0.994	N	0.539	0.288	0.298403945805	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.92976E-04	None	0	0	0	0	0
G/E	rs2154295843	None	0.994	N	0.539	0.288	0.298403945805	gnomAD-4.0.0	6.57056E-06	None	None	None	None	N	None	0	0	None	0	1.93424E-04	None	0	0	0	0	0
G/V	None	None	0.994	N	0.64	0.268	0.512192450023	gnomAD-4.0.0	1.59129E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43283E-05	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	0.2277	likely_benign	0.2595	benign	-0.382	Destabilizing	0.198	N	0.252	neutral	N	0.475181024	None	None	N
G/C	0.4725	ambiguous	0.5224	ambiguous	-0.691	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	N
G/D	0.2157	likely_benign	0.2999	benign	-0.509	Destabilizing	0.99	D	0.491	neutral	None	None	None	None	N
G/E	0.2615	likely_benign	0.2951	benign	-0.562	Destabilizing	0.994	D	0.539	neutral	N	0.447743706	None	None	N
G/F	0.8256	likely_pathogenic	0.8583	pathogenic	-0.703	Destabilizing	0.999	D	0.664	neutral	None	None	None	None	N
G/H	0.5961	likely_pathogenic	0.6646	pathogenic	-0.948	Destabilizing	0.999	D	0.582	neutral	None	None	None	None	N
G/I	0.7237	likely_pathogenic	0.7759	pathogenic	-0.033	Destabilizing	0.998	D	0.674	neutral	None	None	None	None	N
G/K	0.5095	ambiguous	0.5522	ambiguous	-0.921	Destabilizing	0.995	D	0.54	neutral	None	None	None	None	N
G/L	0.6901	likely_pathogenic	0.7394	pathogenic	-0.033	Destabilizing	0.995	D	0.637	neutral	None	None	None	None	N
G/M	0.7178	likely_pathogenic	0.7559	pathogenic	-0.14	Destabilizing	1.0	D	0.649	neutral	None	None	None	None	N
G/N	0.2884	likely_benign	0.3297	benign	-0.64	Destabilizing	0.643	D	0.251	neutral	None	None	None	None	N
G/P	0.9783	likely_pathogenic	0.988	pathogenic	-0.107	Destabilizing	0.998	D	0.586	neutral	None	None	None	None	N
G/Q	0.4526	ambiguous	0.4866	ambiguous	-0.763	Destabilizing	0.998	D	0.597	neutral	None	None	None	None	N
G/R	0.4153	ambiguous	0.4603	ambiguous	-0.677	Destabilizing	0.997	D	0.585	neutral	N	0.507138726	None	None	N
G/S	0.1679	likely_benign	0.2071	benign	-0.93	Destabilizing	0.967	D	0.44	neutral	None	None	None	None	N
G/T	0.4635	ambiguous	0.525	ambiguous	-0.89	Destabilizing	0.995	D	0.541	neutral	None	None	None	None	N
G/V	0.5348	ambiguous	0.609	pathogenic	-0.107	Destabilizing	0.994	D	0.64	neutral	N	0.495268294	None	None	N
G/W	0.6514	likely_pathogenic	0.7355	pathogenic	-1.09	Destabilizing	1.0	D	0.615	neutral	None	None	None	None	N
G/Y	0.6304	likely_pathogenic	0.6993	pathogenic	-0.626	Destabilizing	1.0	D	0.661	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.