TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17688	53287;53288;53289	chr2:178607626;178607625;178607624	chr2:179472353;179472352;179472351
N2AB	16047	48364;48365;48366	chr2:178607626;178607625;178607624	chr2:179472353;179472352;179472351
N2A	15120	45583;45584;45585	chr2:178607626;178607625;178607624	chr2:179472353;179472352;179472351
N2B	8623	26092;26093;26094	chr2:178607626;178607625;178607624	chr2:179472353;179472352;179472351
Novex-1	8748	26467;26468;26469	chr2:178607626;178607625;178607624	chr2:179472353;179472352;179472351
Novex-2	8815	26668;26669;26670	chr2:178607626;178607625;178607624	chr2:179472353;179472352;179472351
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-113
• Domain position: 12
• Structural Position: 25
• Q(SASA): 0.4709
• 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/E	rs201675016	0.056	None	N	0.101	0.073	None	gnomAD-4.0.0	9.23365E-04	None	None	None	None	N	None	0	4.57561E-05	None	0	2.77994E-05	None	9.57504E-03	0	8.29785E-05	0	1.36629E-03

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	0.3611	ambiguous	0.3114	benign	-0.152	Destabilizing	0.055	N	0.367	neutral	None	None	None	None	N
K/C	0.685	likely_pathogenic	0.5984	pathogenic	-0.072	Destabilizing	0.958	D	0.361	neutral	None	None	None	None	N
K/D	0.4446	ambiguous	0.4007	ambiguous	0.014	Stabilizing	0.055	N	0.364	neutral	None	None	None	None	N
K/E	0.1442	likely_benign	0.1266	benign	0.044	Stabilizing	None	N	0.101	neutral	N	0.343034897	None	None	N
K/F	0.8733	likely_pathogenic	0.8154	pathogenic	-0.222	Destabilizing	0.859	D	0.369	neutral	None	None	None	None	N
K/G	0.4312	ambiguous	0.3666	ambiguous	-0.416	Destabilizing	0.22	N	0.373	neutral	None	None	None	None	N
K/H	0.3126	likely_benign	0.2718	benign	-0.848	Destabilizing	0.497	N	0.331	neutral	None	None	None	None	N
K/I	0.5902	likely_pathogenic	0.5112	ambiguous	0.481	Stabilizing	0.667	D	0.402	neutral	None	None	None	None	N
K/L	0.4997	ambiguous	0.4222	ambiguous	0.481	Stabilizing	0.22	N	0.376	neutral	None	None	None	None	N
K/M	0.2927	likely_benign	0.244	benign	0.419	Stabilizing	0.602	D	0.337	neutral	N	0.501962193	None	None	N
K/N	0.294	likely_benign	0.2539	benign	0.176	Stabilizing	0.175	N	0.301	neutral	N	0.42003703	None	None	N
K/P	0.9805	likely_pathogenic	0.9718	pathogenic	0.3	Stabilizing	0.364	N	0.401	neutral	None	None	None	None	N
K/Q	0.0951	likely_benign	0.0859	benign	-0.004	Destabilizing	None	N	0.101	neutral	N	0.406337014	None	None	N
K/R	0.1045	likely_benign	0.0957	benign	-0.192	Destabilizing	0.042	N	0.354	neutral	N	0.44048966	None	None	N
K/S	0.3177	likely_benign	0.2733	benign	-0.351	Destabilizing	0.055	N	0.349	neutral	None	None	None	None	N
K/T	0.1807	likely_benign	0.1544	benign	-0.154	Destabilizing	0.175	N	0.361	neutral	N	0.428829872	None	None	N
K/V	0.4612	ambiguous	0.3935	ambiguous	0.3	Stabilizing	0.22	N	0.383	neutral	None	None	None	None	N
K/W	0.8982	likely_pathogenic	0.8505	pathogenic	-0.182	Destabilizing	0.958	D	0.37	neutral	None	None	None	None	N
K/Y	0.7088	likely_pathogenic	0.6359	pathogenic	0.148	Stabilizing	0.667	D	0.367	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.