TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23675	71248;71249;71250	chr2:178575109;178575108;178575107	chr2:179439836;179439835;179439834
N2AB	22034	66325;66326;66327	chr2:178575109;178575108;178575107	chr2:179439836;179439835;179439834
N2A	21107	63544;63545;63546	chr2:178575109;178575108;178575107	chr2:179439836;179439835;179439834
N2B	14610	44053;44054;44055	chr2:178575109;178575108;178575107	chr2:179439836;179439835;179439834
Novex-1	14735	44428;44429;44430	chr2:178575109;178575108;178575107	chr2:179439836;179439835;179439834
Novex-2	14802	44629;44630;44631	chr2:178575109;178575108;178575107	chr2:179439836;179439835;179439834
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-130
• Domain position: 39
• Structural Position: 59
• Q(SASA): 0.7899
• 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
K/N	None	None	0.978	N	0.637	0.286	0.27132560031	gnomAD-4.0.0	1.59279E-06	None	None	None	None	N	None	0	0	None	0	2.78816E-05	None	0	0	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
K/A	0.6524	likely_pathogenic	0.6567	pathogenic	-0.002	Destabilizing	0.944	D	0.623	neutral	None	None	None	None	N
K/C	0.7955	likely_pathogenic	0.8008	pathogenic	-0.539	Destabilizing	0.999	D	0.721	prob.delet.	None	None	None	None	N
K/D	0.8856	likely_pathogenic	0.8893	pathogenic	-0.193	Destabilizing	0.983	D	0.675	prob.neutral	None	None	None	None	N
K/E	0.4779	ambiguous	0.4624	ambiguous	-0.179	Destabilizing	0.928	D	0.593	neutral	N	0.453809327	None	None	N
K/F	0.8948	likely_pathogenic	0.8955	pathogenic	-0.289	Destabilizing	0.999	D	0.701	prob.neutral	None	None	None	None	N
K/G	0.72	likely_pathogenic	0.7296	pathogenic	-0.159	Destabilizing	0.983	D	0.579	neutral	None	None	None	None	N
K/H	0.386	ambiguous	0.4005	ambiguous	-0.228	Destabilizing	0.998	D	0.662	neutral	None	None	None	None	N
K/I	0.5712	likely_pathogenic	0.5689	pathogenic	0.333	Stabilizing	0.989	D	0.709	prob.delet.	N	0.520997111	None	None	N
K/L	0.5213	ambiguous	0.5246	ambiguous	0.333	Stabilizing	0.983	D	0.579	neutral	None	None	None	None	N
K/M	0.4711	ambiguous	0.4648	ambiguous	-0.16	Destabilizing	0.999	D	0.66	neutral	None	None	None	None	N
K/N	0.7728	likely_pathogenic	0.7804	pathogenic	-0.125	Destabilizing	0.978	D	0.637	neutral	N	0.49584795	None	None	N
K/P	0.7535	likely_pathogenic	0.7403	pathogenic	0.246	Stabilizing	0.997	D	0.657	neutral	None	None	None	None	N
K/Q	0.1939	likely_benign	0.193	benign	-0.197	Destabilizing	0.978	D	0.627	neutral	N	0.498061536	None	None	N
K/R	0.0851	likely_benign	0.0846	benign	-0.1	Destabilizing	0.085	N	0.355	neutral	N	0.485054953	None	None	N
K/S	0.7239	likely_pathogenic	0.7336	pathogenic	-0.485	Destabilizing	0.944	D	0.595	neutral	None	None	None	None	N
K/T	0.4286	ambiguous	0.428	ambiguous	-0.336	Destabilizing	0.978	D	0.623	neutral	N	0.457657708	None	None	N
K/V	0.5378	ambiguous	0.536	ambiguous	0.246	Stabilizing	0.992	D	0.684	prob.neutral	None	None	None	None	N
K/W	0.8509	likely_pathogenic	0.8428	pathogenic	-0.408	Destabilizing	0.999	D	0.728	prob.delet.	None	None	None	None	N
K/Y	0.7893	likely_pathogenic	0.787	pathogenic	-0.046	Destabilizing	0.997	D	0.678	prob.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.