TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16312	49159;49160;49161	chr2:178614580;178614579;178614578	chr2:179479307;179479306;179479305
N2AB	14671	44236;44237;44238	chr2:178614580;178614579;178614578	chr2:179479307;179479306;179479305
N2A	13744	41455;41456;41457	chr2:178614580;178614579;178614578	chr2:179479307;179479306;179479305
N2B	7247	21964;21965;21966	chr2:178614580;178614579;178614578	chr2:179479307;179479306;179479305
Novex-1	7372	22339;22340;22341	chr2:178614580;178614579;178614578	chr2:179479307;179479306;179479305
Novex-2	7439	22540;22541;22542	chr2:178614580;178614579;178614578	chr2:179479307;179479306;179479305
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: Ig-110
• Domain position: 51
• Structural Position: 134
• Q(SASA): 0.5087
• 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	None	N	0.137	0.115	0.0551355673512	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
K/A	0.3761	ambiguous	0.3635	ambiguous	-0.052	Destabilizing	0.129	N	0.365	neutral	None	None	None	None	N
K/C	0.652	likely_pathogenic	0.6325	pathogenic	-0.195	Destabilizing	0.983	D	0.493	neutral	None	None	None	None	N
K/D	0.5669	likely_pathogenic	0.5216	ambiguous	0.059	Stabilizing	0.129	N	0.421	neutral	None	None	None	None	N
K/E	0.2439	likely_benign	0.2153	benign	0.102	Stabilizing	0.183	N	0.279	neutral	N	0.494041351	None	None	N
K/F	0.8288	likely_pathogenic	0.8367	pathogenic	-0.026	Destabilizing	0.94	D	0.513	neutral	None	None	None	None	N
K/G	0.2313	likely_benign	0.2149	benign	-0.32	Destabilizing	None	N	0.237	neutral	None	None	None	None	N
K/H	0.3604	ambiguous	0.3412	ambiguous	-0.635	Destabilizing	0.716	D	0.46	neutral	None	None	None	None	N
K/I	0.6332	likely_pathogenic	0.6636	pathogenic	0.594	Stabilizing	0.836	D	0.517	neutral	None	None	None	None	N
K/L	0.4746	ambiguous	0.4739	ambiguous	0.594	Stabilizing	0.418	N	0.493	neutral	None	None	None	None	N
K/M	0.3325	likely_benign	0.3338	benign	0.296	Stabilizing	0.921	D	0.457	neutral	N	0.515077874	None	None	N
K/N	0.3992	ambiguous	0.3786	ambiguous	0.07	Stabilizing	None	N	0.137	neutral	N	0.460287045	None	None	N
K/P	0.7901	likely_pathogenic	0.7778	pathogenic	0.409	Stabilizing	0.593	D	0.469	neutral	None	None	None	None	N
K/Q	0.1456	likely_benign	0.1364	benign	-0.042	Destabilizing	0.351	N	0.363	neutral	N	0.506954722	None	None	N
K/R	0.0902	likely_benign	0.0888	benign	-0.254	Destabilizing	0.351	N	0.272	neutral	N	0.50846802	None	None	N
K/S	0.4026	ambiguous	0.3737	ambiguous	-0.421	Destabilizing	0.129	N	0.259	neutral	None	None	None	None	N
K/T	0.277	likely_benign	0.2711	benign	-0.212	Destabilizing	0.351	N	0.404	neutral	N	0.483783015	None	None	N
K/V	0.5214	ambiguous	0.5355	ambiguous	0.409	Stabilizing	0.593	D	0.518	neutral	None	None	None	None	N
K/W	0.8264	likely_pathogenic	0.8222	pathogenic	-0.02	Destabilizing	0.983	D	0.514	neutral	None	None	None	None	N
K/Y	0.6673	likely_pathogenic	0.6761	pathogenic	0.299	Stabilizing	0.94	D	0.504	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.