TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31439	94540;94541;94542	chr2:178547210;178547209;178547208	chr2:179411937;179411936;179411935
N2AB	29798	89617;89618;89619	chr2:178547210;178547209;178547208	chr2:179411937;179411936;179411935
N2A	28871	86836;86837;86838	chr2:178547210;178547209;178547208	chr2:179411937;179411936;179411935
N2B	22374	67345;67346;67347	chr2:178547210;178547209;178547208	chr2:179411937;179411936;179411935
Novex-1	22499	67720;67721;67722	chr2:178547210;178547209;178547208	chr2:179411937;179411936;179411935
Novex-2	22566	67921;67922;67923	chr2:178547210;178547209;178547208	chr2:179411937;179411936;179411935
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: Fn3-117
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.6608
• Predicted PPI site: I

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/E	None	None	0.956	N	0.561	0.29	0.253726318573	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
K/A	0.2614	likely_benign	0.2812	benign	0.033	Stabilizing	0.983	D	0.624	neutral	None	None	None	None	I
K/C	0.6032	likely_pathogenic	0.6452	pathogenic	-0.256	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	I
K/D	0.4388	ambiguous	0.4869	ambiguous	-0.102	Destabilizing	0.995	D	0.583	neutral	None	None	None	None	I
K/E	0.1491	likely_benign	0.1723	benign	-0.106	Destabilizing	0.956	D	0.561	neutral	N	0.43293733	None	None	I
K/F	0.8233	likely_pathogenic	0.8582	pathogenic	-0.259	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	I
K/G	0.3952	ambiguous	0.4199	ambiguous	-0.126	Destabilizing	0.998	D	0.563	neutral	None	None	None	None	I
K/H	0.282	likely_benign	0.3014	benign	-0.295	Destabilizing	0.999	D	0.612	neutral	None	None	None	None	I
K/I	0.4377	ambiguous	0.5052	ambiguous	0.37	Stabilizing	0.999	D	0.703	prob.neutral	N	0.512555694	None	None	I
K/L	0.3871	ambiguous	0.4209	ambiguous	0.37	Stabilizing	0.995	D	0.563	neutral	None	None	None	None	I
K/M	0.3007	likely_benign	0.3304	benign	0.079	Stabilizing	1.0	D	0.611	neutral	None	None	None	None	I
K/N	0.3357	likely_benign	0.3852	ambiguous	0.197	Stabilizing	0.997	D	0.609	neutral	N	0.493449858	None	None	I
K/P	0.2596	likely_benign	0.2749	benign	0.283	Stabilizing	0.999	D	0.648	neutral	None	None	None	None	I
K/Q	0.1179	likely_benign	0.1221	benign	0.042	Stabilizing	0.63	D	0.284	neutral	N	0.493103142	None	None	I
K/R	0.0755	likely_benign	0.0744	benign	0.008	Stabilizing	0.978	D	0.533	neutral	N	0.446389417	None	None	I
K/S	0.3262	likely_benign	0.3568	ambiguous	-0.22	Destabilizing	0.983	D	0.599	neutral	None	None	None	None	I
K/T	0.1791	likely_benign	0.2029	benign	-0.091	Destabilizing	0.997	D	0.577	neutral	N	0.472997228	None	None	I
K/V	0.3342	likely_benign	0.3739	ambiguous	0.283	Stabilizing	0.998	D	0.614	neutral	None	None	None	None	I
K/W	0.8003	likely_pathogenic	0.8236	pathogenic	-0.331	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
K/Y	0.6801	likely_pathogenic	0.7273	pathogenic	0.028	Stabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	I

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.