TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21311	64156;64157;64158	chr2:178587280;178587279;178587278	chr2:179452007;179452006;179452005
N2AB	19670	59233;59234;59235	chr2:178587280;178587279;178587278	chr2:179452007;179452006;179452005
N2A	18743	56452;56453;56454	chr2:178587280;178587279;178587278	chr2:179452007;179452006;179452005
N2B	12246	36961;36962;36963	chr2:178587280;178587279;178587278	chr2:179452007;179452006;179452005
Novex-1	12371	37336;37337;37338	chr2:178587280;178587279;178587278	chr2:179452007;179452006;179452005
Novex-2	12438	37537;37538;37539	chr2:178587280;178587279;178587278	chr2:179452007;179452006;179452005
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-42
• Domain position: 46
• Structural Position: 63
• Q(SASA): 0.9092
• 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/R	rs375535453	None	0.999	N	0.592	0.309	None	gnomAD-4.0.0	1.59255E-06	None	None	None	None	N	None	5.66701E-05	0	None	0	0	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	0.8394	likely_pathogenic	0.8226	pathogenic	-0.016	Destabilizing	0.999	D	0.619	neutral	None	None	None	None	N
K/C	0.9131	likely_pathogenic	0.9057	pathogenic	-0.512	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
K/D	0.9415	likely_pathogenic	0.9313	pathogenic	-0.256	Destabilizing	1.0	D	0.635	neutral	None	None	None	None	N
K/E	0.7492	likely_pathogenic	0.7197	pathogenic	-0.273	Destabilizing	0.999	D	0.641	neutral	N	0.478477619	None	None	N
K/F	0.9587	likely_pathogenic	0.9596	pathogenic	-0.382	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
K/G	0.8593	likely_pathogenic	0.8212	pathogenic	-0.129	Destabilizing	1.0	D	0.605	neutral	None	None	None	None	N
K/H	0.628	likely_pathogenic	0.5938	pathogenic	-0.214	Destabilizing	1.0	D	0.66	neutral	None	None	None	None	N
K/I	0.8263	likely_pathogenic	0.8417	pathogenic	0.196	Stabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
K/L	0.7196	likely_pathogenic	0.7229	pathogenic	0.196	Stabilizing	1.0	D	0.605	neutral	None	None	None	None	N
K/M	0.6088	likely_pathogenic	0.6208	pathogenic	-0.126	Destabilizing	1.0	D	0.657	neutral	N	0.500010471	None	None	N
K/N	0.872	likely_pathogenic	0.8645	pathogenic	-0.049	Destabilizing	1.0	D	0.662	neutral	N	0.481133922	None	None	N
K/P	0.895	likely_pathogenic	0.889	pathogenic	0.148	Stabilizing	1.0	D	0.623	neutral	None	None	None	None	N
K/Q	0.385	ambiguous	0.3583	ambiguous	-0.189	Destabilizing	1.0	D	0.653	neutral	N	0.505722935	None	None	N
K/R	0.1115	likely_benign	0.1072	benign	-0.144	Destabilizing	0.999	D	0.592	neutral	N	0.457721132	None	None	N
K/S	0.891	likely_pathogenic	0.8764	pathogenic	-0.422	Destabilizing	0.999	D	0.613	neutral	None	None	None	None	N
K/T	0.7001	likely_pathogenic	0.6936	pathogenic	-0.327	Destabilizing	1.0	D	0.619	neutral	N	0.470957001	None	None	N
K/V	0.7739	likely_pathogenic	0.7862	pathogenic	0.148	Stabilizing	1.0	D	0.655	neutral	None	None	None	None	N
K/W	0.9442	likely_pathogenic	0.938	pathogenic	-0.484	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
K/Y	0.9023	likely_pathogenic	0.8939	pathogenic	-0.131	Destabilizing	1.0	D	0.679	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.