TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21274	64045;64046;64047	chr2:178587391;178587390;178587389	chr2:179452118;179452117;179452116
N2AB	19633	59122;59123;59124	chr2:178587391;178587390;178587389	chr2:179452118;179452117;179452116
N2A	18706	56341;56342;56343	chr2:178587391;178587390;178587389	chr2:179452118;179452117;179452116
N2B	12209	36850;36851;36852	chr2:178587391;178587390;178587389	chr2:179452118;179452117;179452116
Novex-1	12334	37225;37226;37227	chr2:178587391;178587390;178587389	chr2:179452118;179452117;179452116
Novex-2	12401	37426;37427;37428	chr2:178587391;178587390;178587389	chr2:179452118;179452117;179452116
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: Fn3-42
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.5329
• 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	rs886042547	None	0.001	N	0.205	0.115	0.199424873507	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	0
K/T	None	None	0.003	N	0.367	0.155	0.241078983079	gnomAD-4.0.0	1.59787E-06	None	None	None	None	N	None	0	0	None	0	2.79814E-05	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	0.1548	likely_benign	0.2046	benign	-0.327	Destabilizing	0.055	N	0.445	neutral	None	None	None	None	N
K/C	0.302	likely_benign	0.3879	ambiguous	-0.486	Destabilizing	0.958	D	0.483	neutral	None	None	None	None	N
K/D	0.3272	likely_benign	0.4355	ambiguous	0.199	Stabilizing	None	N	0.299	neutral	None	None	None	None	N
K/E	0.1208	likely_benign	0.1523	benign	0.248	Stabilizing	0.001	N	0.205	neutral	N	0.388650622	None	None	N
K/F	0.4085	ambiguous	0.5082	ambiguous	-0.354	Destabilizing	0.667	D	0.485	neutral	None	None	None	None	N
K/G	0.2555	likely_benign	0.3478	ambiguous	-0.6	Destabilizing	0.22	N	0.483	neutral	None	None	None	None	N
K/H	0.133	likely_benign	0.1589	benign	-0.933	Destabilizing	0.497	N	0.525	neutral	None	None	None	None	N
K/I	0.1549	likely_benign	0.1924	benign	0.334	Stabilizing	0.427	N	0.525	neutral	N	0.445986772	None	None	N
K/L	0.1613	likely_benign	0.2071	benign	0.334	Stabilizing	0.124	N	0.52	neutral	None	None	None	None	N
K/M	0.1148	likely_benign	0.1419	benign	0.203	Stabilizing	0.667	D	0.529	neutral	None	None	None	None	N
K/N	0.1952	likely_benign	0.2792	benign	-0.097	Destabilizing	0.175	N	0.44	neutral	N	0.481734142	None	None	N
K/P	0.7475	likely_pathogenic	0.8531	pathogenic	0.144	Stabilizing	0.364	N	0.56	neutral	None	None	None	None	N
K/Q	0.0822	likely_benign	0.0937	benign	-0.258	Destabilizing	0.003	N	0.323	neutral	N	0.431862682	None	None	N
K/R	0.0728	likely_benign	0.0763	benign	-0.272	Destabilizing	0.001	N	0.269	neutral	N	0.398827544	None	None	N
K/S	0.1709	likely_benign	0.2448	benign	-0.742	Destabilizing	0.055	N	0.449	neutral	None	None	None	None	N
K/T	0.0777	likely_benign	0.0972	benign	-0.51	Destabilizing	0.003	N	0.367	neutral	N	0.423549843	None	None	N
K/V	0.1367	likely_benign	0.1666	benign	0.144	Stabilizing	0.124	N	0.515	neutral	None	None	None	None	N
K/W	0.4451	ambiguous	0.5404	ambiguous	-0.25	Destabilizing	0.958	D	0.518	neutral	None	None	None	None	N
K/Y	0.325	likely_benign	0.4149	ambiguous	0.077	Stabilizing	0.667	D	0.488	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.