TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23482	70669;70670;70671	chr2:178575688;178575687;178575686	chr2:179440415;179440414;179440413
N2AB	21841	65746;65747;65748	chr2:178575688;178575687;178575686	chr2:179440415;179440414;179440413
N2A	20914	62965;62966;62967	chr2:178575688;178575687;178575686	chr2:179440415;179440414;179440413
N2B	14417	43474;43475;43476	chr2:178575688;178575687;178575686	chr2:179440415;179440414;179440413
Novex-1	14542	43849;43850;43851	chr2:178575688;178575687;178575686	chr2:179440415;179440414;179440413
Novex-2	14609	44050;44051;44052	chr2:178575688;178575687;178575686	chr2:179440415;179440414;179440413
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: Fn3-58
• Domain position: 48
• Structural Position: 65
• Q(SASA): 0.1906
• 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
Y/F	None	None	0.965	N	0.47	0.279	0.415690173769	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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	0.9882	likely_pathogenic	0.9872	pathogenic	-2.524	Highly Destabilizing	0.987	D	0.505	neutral	None	None	None	None	N
Y/C	0.8703	likely_pathogenic	0.8628	pathogenic	-1.112	Destabilizing	0.452	N	0.44	neutral	N	0.494041715	None	None	N
Y/D	0.9888	likely_pathogenic	0.9872	pathogenic	-0.908	Destabilizing	1.0	D	0.701	prob.neutral	N	0.479985931	None	None	N
Y/E	0.9988	likely_pathogenic	0.9985	pathogenic	-0.841	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	N
Y/F	0.1008	likely_benign	0.0979	benign	-1.324	Destabilizing	0.965	D	0.47	neutral	N	0.4617988	None	None	N
Y/G	0.9849	likely_pathogenic	0.9828	pathogenic	-2.808	Highly Destabilizing	0.999	D	0.695	prob.neutral	None	None	None	None	N
Y/H	0.8835	likely_pathogenic	0.8619	pathogenic	-0.999	Destabilizing	0.999	D	0.644	neutral	N	0.504891042	None	None	N
Y/I	0.977	likely_pathogenic	0.9759	pathogenic	-1.67	Destabilizing	0.953	D	0.623	neutral	None	None	None	None	N
Y/K	0.9985	likely_pathogenic	0.9981	pathogenic	-1.024	Destabilizing	0.992	D	0.666	neutral	None	None	None	None	N
Y/L	0.9586	likely_pathogenic	0.9521	pathogenic	-1.67	Destabilizing	0.745	D	0.489	neutral	None	None	None	None	N
Y/M	0.9847	likely_pathogenic	0.9813	pathogenic	-1.304	Destabilizing	1.0	D	0.651	neutral	None	None	None	None	N
Y/N	0.9611	likely_pathogenic	0.9557	pathogenic	-1.212	Destabilizing	1.0	D	0.671	neutral	N	0.487040276	None	None	N
Y/P	0.9893	likely_pathogenic	0.9866	pathogenic	-1.949	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
Y/Q	0.9968	likely_pathogenic	0.9959	pathogenic	-1.285	Destabilizing	0.999	D	0.671	neutral	None	None	None	None	N
Y/R	0.9941	likely_pathogenic	0.9927	pathogenic	-0.4	Destabilizing	0.999	D	0.676	prob.neutral	None	None	None	None	N
Y/S	0.9523	likely_pathogenic	0.9479	pathogenic	-1.861	Destabilizing	0.997	D	0.613	neutral	N	0.473656055	None	None	N
Y/T	0.9914	likely_pathogenic	0.9899	pathogenic	-1.707	Destabilizing	0.998	D	0.644	neutral	None	None	None	None	N
Y/V	0.9629	likely_pathogenic	0.9614	pathogenic	-1.949	Destabilizing	0.993	D	0.531	neutral	None	None	None	None	N
Y/W	0.2846	likely_benign	0.2497	benign	-0.798	Destabilizing	1.0	D	0.627	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.