TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31344	94255;94256;94257	chr2:178547596;178547595;178547594	chr2:179412323;179412322;179412321
N2AB	29703	89332;89333;89334	chr2:178547596;178547595;178547594	chr2:179412323;179412322;179412321
N2A	28776	86551;86552;86553	chr2:178547596;178547595;178547594	chr2:179412323;179412322;179412321
N2B	22279	67060;67061;67062	chr2:178547596;178547595;178547594	chr2:179412323;179412322;179412321
Novex-1	22404	67435;67436;67437	chr2:178547596;178547595;178547594	chr2:179412323;179412322;179412321
Novex-2	22471	67636;67637;67638	chr2:178547596;178547595;178547594	chr2:179412323;179412322;179412321
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Fn3-116
• Domain position: 37
• Structural Position: 38
• Q(SASA): 0.082
• 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/H	None	None	1.0	D	0.819	0.872	0.72228197777	gnomAD-4.0.0	6.8418E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99444E-07	0	0
Y/N	rs1697758190	None	1.0	D	0.899	0.88	0.887742029288	gnomAD-4.0.0	6.8418E-07	None	None	None	None	N	None	0	0	None	0	2.51953E-05	None	0	0	0	0	0
Y/S	rs762341884	-3.428	1.0	D	0.911	0.889	0.893281903486	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	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	0.9965	likely_pathogenic	0.995	pathogenic	-3.809	Highly Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
Y/C	0.9259	likely_pathogenic	0.8944	pathogenic	-2.112	Highly Destabilizing	1.0	D	0.871	deleterious	D	0.641190108	None	None	N
Y/D	0.9942	likely_pathogenic	0.9945	pathogenic	-3.833	Highly Destabilizing	1.0	D	0.916	deleterious	D	0.641593717	None	None	N
Y/E	0.9991	likely_pathogenic	0.999	pathogenic	-3.625	Highly Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
Y/F	0.2989	likely_benign	0.2536	benign	-1.563	Destabilizing	0.999	D	0.649	neutral	D	0.557814433	None	None	N
Y/G	0.9935	likely_pathogenic	0.9906	pathogenic	-4.188	Highly Destabilizing	1.0	D	0.928	deleterious	None	None	None	None	N
Y/H	0.9519	likely_pathogenic	0.9414	pathogenic	-2.8	Highly Destabilizing	1.0	D	0.819	deleterious	D	0.641190108	None	None	N
Y/I	0.9798	likely_pathogenic	0.9773	pathogenic	-2.509	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
Y/K	0.9985	likely_pathogenic	0.9982	pathogenic	-2.491	Highly Destabilizing	1.0	D	0.904	deleterious	None	None	None	None	N
Y/L	0.9633	likely_pathogenic	0.9554	pathogenic	-2.509	Highly Destabilizing	0.999	D	0.765	deleterious	None	None	None	None	N
Y/M	0.9895	likely_pathogenic	0.9872	pathogenic	-2.265	Highly Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
Y/N	0.9652	likely_pathogenic	0.9654	pathogenic	-3.182	Highly Destabilizing	1.0	D	0.899	deleterious	D	0.641593717	None	None	N
Y/P	0.9996	likely_pathogenic	0.9995	pathogenic	-2.963	Highly Destabilizing	1.0	D	0.941	deleterious	None	None	None	None	N
Y/Q	0.9976	likely_pathogenic	0.997	pathogenic	-2.961	Highly Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
Y/R	0.992	likely_pathogenic	0.9903	pathogenic	-2.19	Highly Destabilizing	1.0	D	0.898	deleterious	None	None	None	None	N
Y/S	0.983	likely_pathogenic	0.9804	pathogenic	-3.515	Highly Destabilizing	1.0	D	0.911	deleterious	D	0.641593717	None	None	N
Y/T	0.9929	likely_pathogenic	0.9918	pathogenic	-3.194	Highly Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
Y/V	0.959	likely_pathogenic	0.9512	pathogenic	-2.963	Highly Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
Y/W	0.8764	likely_pathogenic	0.8596	pathogenic	-0.703	Destabilizing	1.0	D	0.801	deleterious	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.