TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21532	64819;64820;64821	chr2:178585150;178585149;178585148	chr2:179449877;179449876;179449875
N2AB	19891	59896;59897;59898	chr2:178585150;178585149;178585148	chr2:179449877;179449876;179449875
N2A	18964	57115;57116;57117	chr2:178585150;178585149;178585148	chr2:179449877;179449876;179449875
N2B	12467	37624;37625;37626	chr2:178585150;178585149;178585148	chr2:179449877;179449876;179449875
Novex-1	12592	37999;38000;38001	chr2:178585150;178585149;178585148	chr2:179449877;179449876;179449875
Novex-2	12659	38200;38201;38202	chr2:178585150;178585149;178585148	chr2:179449877;179449876;179449875
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: Ig-124
• Domain position: 64
• Structural Position: 148
• Q(SASA): 0.8439
• 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	rs794729477	0.079	0.99	N	0.525	0.259	0.1749357433	gnomAD-2.1.1	1.21E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	2.68E-05	0
K/E	rs794729477	0.079	0.99	N	0.525	0.259	0.1749357433	gnomAD-4.0.0	9.55338E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.7163E-05	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	0.2775	likely_benign	0.2154	benign	0.077	Stabilizing	0.469	N	0.309	neutral	None	None	None	None	I
K/C	0.6883	likely_pathogenic	0.6078	pathogenic	-0.118	Destabilizing	1.0	D	0.617	neutral	None	None	None	None	I
K/D	0.4492	ambiguous	0.3709	ambiguous	-0.032	Destabilizing	0.998	D	0.479	neutral	None	None	None	None	I
K/E	0.1671	likely_benign	0.1305	benign	-0.046	Destabilizing	0.99	D	0.525	neutral	N	0.413702917	None	None	I
K/F	0.7928	likely_pathogenic	0.7157	pathogenic	-0.265	Destabilizing	0.999	D	0.614	neutral	None	None	None	None	I
K/G	0.3708	ambiguous	0.2956	benign	-0.071	Destabilizing	0.985	D	0.493	neutral	None	None	None	None	I
K/H	0.3338	likely_benign	0.2851	benign	-0.318	Destabilizing	1.0	D	0.517	neutral	None	None	None	None	I
K/I	0.4188	ambiguous	0.3399	benign	0.381	Stabilizing	0.994	D	0.617	neutral	N	0.504847783	None	None	I
K/L	0.3754	ambiguous	0.2992	benign	0.381	Stabilizing	0.985	D	0.487	neutral	None	None	None	None	I
K/M	0.2456	likely_benign	0.1918	benign	0.193	Stabilizing	1.0	D	0.513	neutral	None	None	None	None	I
K/N	0.3677	ambiguous	0.2933	benign	0.342	Stabilizing	0.997	D	0.511	neutral	N	0.461267577	None	None	I
K/P	0.7399	likely_pathogenic	0.6774	pathogenic	0.305	Stabilizing	0.998	D	0.52	neutral	None	None	None	None	I
K/Q	0.1305	likely_benign	0.1126	benign	0.164	Stabilizing	0.999	D	0.551	neutral	N	0.434851767	None	None	I
K/R	0.0922	likely_benign	0.0877	benign	0.073	Stabilizing	0.99	D	0.504	neutral	N	0.472023288	None	None	I
K/S	0.3393	likely_benign	0.2574	benign	-0.078	Destabilizing	0.971	D	0.496	neutral	None	None	None	None	I
K/T	0.17	likely_benign	0.1298	benign	0.036	Stabilizing	0.4	N	0.351	neutral	N	0.441681739	None	None	I
K/V	0.3665	ambiguous	0.2885	benign	0.305	Stabilizing	0.985	D	0.472	neutral	None	None	None	None	I
K/W	0.7636	likely_pathogenic	0.6997	pathogenic	-0.339	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	I
K/Y	0.6662	likely_pathogenic	0.5857	pathogenic	0.032	Stabilizing	0.999	D	0.577	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.