TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23545	70858;70859;70860	chr2:178575499;178575498;178575497	chr2:179440226;179440225;179440224
N2AB	21904	65935;65936;65937	chr2:178575499;178575498;178575497	chr2:179440226;179440225;179440224
N2A	20977	63154;63155;63156	chr2:178575499;178575498;178575497	chr2:179440226;179440225;179440224
N2B	14480	43663;43664;43665	chr2:178575499;178575498;178575497	chr2:179440226;179440225;179440224
Novex-1	14605	44038;44039;44040	chr2:178575499;178575498;178575497	chr2:179440226;179440225;179440224
Novex-2	14672	44239;44240;44241	chr2:178575499;178575498;178575497	chr2:179440226;179440225;179440224
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-59
• Domain position: 14
• Structural Position: 16
• Q(SASA): 0.1701
• 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
T/I	None	None	0.942	D	0.437	0.479	0.603539076606	gnomAD-4.0.0	6.84245E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99536E-07	0	0
T/S	rs1247049807	-1.204	0.006	N	0.157	0.068	0.154104182512	gnomAD-4.0.0	6.84245E-07	None	None	None	None	N	None	0	2.23604E-05	None	0	0	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
T/A	0.4051	ambiguous	0.3398	benign	-0.848	Destabilizing	0.032	N	0.453	neutral	N	0.49454283	None	None	N
T/C	0.8385	likely_pathogenic	0.8013	pathogenic	-0.742	Destabilizing	0.995	D	0.46	neutral	None	None	None	None	N
T/D	0.6451	likely_pathogenic	0.6322	pathogenic	-1.012	Destabilizing	0.002	N	0.291	neutral	None	None	None	None	N
T/E	0.7965	likely_pathogenic	0.7651	pathogenic	-0.983	Destabilizing	0.521	D	0.415	neutral	None	None	None	None	N
T/F	0.8985	likely_pathogenic	0.8645	pathogenic	-0.889	Destabilizing	0.994	D	0.531	neutral	None	None	None	None	N
T/G	0.299	likely_benign	0.2687	benign	-1.124	Destabilizing	0.845	D	0.451	neutral	None	None	None	None	N
T/H	0.6852	likely_pathogenic	0.6404	pathogenic	-1.407	Destabilizing	0.996	D	0.52	neutral	None	None	None	None	N
T/I	0.9467	likely_pathogenic	0.9297	pathogenic	-0.195	Destabilizing	0.942	D	0.437	neutral	D	0.528891689	None	None	N
T/K	0.6901	likely_pathogenic	0.6279	pathogenic	-0.843	Destabilizing	0.752	D	0.407	neutral	None	None	None	None	N
T/L	0.6295	likely_pathogenic	0.5526	ambiguous	-0.195	Destabilizing	0.86	D	0.426	neutral	None	None	None	None	N
T/M	0.4625	ambiguous	0.4086	ambiguous	0.112	Stabilizing	0.996	D	0.441	neutral	None	None	None	None	N
T/N	0.3233	likely_benign	0.2996	benign	-0.995	Destabilizing	0.197	N	0.421	neutral	N	0.475055769	None	None	N
T/P	0.877	likely_pathogenic	0.8669	pathogenic	-0.381	Destabilizing	0.778	D	0.443	neutral	D	0.528891689	None	None	N
T/Q	0.6043	likely_pathogenic	0.5425	ambiguous	-1.194	Destabilizing	0.91	D	0.441	neutral	None	None	None	None	N
T/R	0.663	likely_pathogenic	0.5856	pathogenic	-0.574	Destabilizing	0.983	D	0.434	neutral	None	None	None	None	N
T/S	0.1373	likely_benign	0.1275	benign	-1.189	Destabilizing	0.006	N	0.157	neutral	N	0.469458278	None	None	N
T/V	0.8576	likely_pathogenic	0.8151	pathogenic	-0.381	Destabilizing	0.815	D	0.427	neutral	None	None	None	None	N
T/W	0.9589	likely_pathogenic	0.9497	pathogenic	-0.851	Destabilizing	0.998	D	0.573	neutral	None	None	None	None	N
T/Y	0.8738	likely_pathogenic	0.8383	pathogenic	-0.578	Destabilizing	0.994	D	0.535	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.