TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34305	103138;103139;103140	chr2:178533702;178533701;178533700	chr2:179398429;179398428;179398427
N2AB	32664	98215;98216;98217	chr2:178533702;178533701;178533700	chr2:179398429;179398428;179398427
N2A	31737	95434;95435;95436	chr2:178533702;178533701;178533700	chr2:179398429;179398428;179398427
N2B	25240	75943;75944;75945	chr2:178533702;178533701;178533700	chr2:179398429;179398428;179398427
Novex-1	25365	76318;76319;76320	chr2:178533702;178533701;178533700	chr2:179398429;179398428;179398427
Novex-2	25432	76519;76520;76521	chr2:178533702;178533701;178533700	chr2:179398429;179398428;179398427
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-161
• Domain position: 48
• Structural Position: 114
• Q(SASA): 0.3946
• 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	rs2154135333	None	None	N	0.134	0.074	0.0884992946249	gnomAD-4.0.0	1.59102E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85763E-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	0.1794	likely_benign	0.1633	benign	0.083	Stabilizing	None	N	0.155	neutral	None	None	None	None	N
K/C	0.497	ambiguous	0.4831	ambiguous	-0.244	Destabilizing	0.824	D	0.309	neutral	None	None	None	None	N
K/D	0.2812	likely_benign	0.2409	benign	-0.18	Destabilizing	0.149	N	0.367	neutral	None	None	None	None	N
K/E	0.1051	likely_benign	0.1007	benign	-0.194	Destabilizing	0.027	N	0.242	neutral	N	0.445208486	None	None	N
K/F	0.6179	likely_pathogenic	0.5566	ambiguous	-0.241	Destabilizing	0.555	D	0.325	neutral	None	None	None	None	N
K/G	0.1913	likely_benign	0.1696	benign	-0.058	Destabilizing	None	N	0.195	neutral	None	None	None	None	N
K/H	0.22	likely_benign	0.206	benign	-0.205	Destabilizing	0.555	D	0.276	neutral	None	None	None	None	N
K/I	0.259	likely_benign	0.2388	benign	0.368	Stabilizing	0.38	N	0.369	neutral	None	None	None	None	N
K/L	0.222	likely_benign	0.205	benign	0.368	Stabilizing	0.081	N	0.354	neutral	None	None	None	None	N
K/M	0.1754	likely_benign	0.1642	benign	0.072	Stabilizing	0.741	D	0.279	neutral	D	0.522439906	None	None	N
K/N	0.2129	likely_benign	0.1803	benign	0.23	Stabilizing	0.117	N	0.214	neutral	N	0.486209747	None	None	N
K/P	0.3862	ambiguous	0.3742	ambiguous	0.297	Stabilizing	0.555	D	0.333	neutral	None	None	None	None	N
K/Q	0.0981	likely_benign	0.0949	benign	0.061	Stabilizing	0.117	N	0.279	neutral	N	0.474336528	None	None	N
K/R	0.0697	likely_benign	0.075	benign	0.029	Stabilizing	None	N	0.134	neutral	N	0.452289174	None	None	N
K/S	0.2023	likely_benign	0.1749	benign	-0.157	Destabilizing	0.007	N	0.147	neutral	None	None	None	None	N
K/T	0.1097	likely_benign	0.1055	benign	-0.051	Destabilizing	0.062	N	0.329	neutral	N	0.441842894	None	None	N
K/V	0.2334	likely_benign	0.2191	benign	0.297	Stabilizing	0.081	N	0.388	neutral	None	None	None	None	N
K/W	0.5429	ambiguous	0.5484	ambiguous	-0.328	Destabilizing	0.935	D	0.336	neutral	None	None	None	None	N
K/Y	0.4611	ambiguous	0.4214	ambiguous	0.032	Stabilizing	0.555	D	0.305	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.