TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13764	41515;41516;41517	chr2:178636437;178636436;178636435	chr2:179501164;179501163;179501162
N2AB	12123	36592;36593;36594	chr2:178636437;178636436;178636435	chr2:179501164;179501163;179501162
N2A	11196	33811;33812;33813	chr2:178636437;178636436;178636435	chr2:179501164;179501163;179501162
N2B	4699	14320;14321;14322	chr2:178636437;178636436;178636435	chr2:179501164;179501163;179501162
Novex-1	4824	14695;14696;14697	chr2:178636437;178636436;178636435	chr2:179501164;179501163;179501162
Novex-2	4891	14896;14897;14898	chr2:178636437;178636436;178636435	chr2:179501164;179501163;179501162
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-87
• Domain position: 81
• Structural Position: 163
• Q(SASA): 0.5633
• 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
N/K	rs1417225547	0.475	0.238	N	0.227	0.143	0.173771789658	gnomAD-4.0.0	3.19518E-06	None	None	None	None	I	None	0	4.5958E-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
N/A	0.5754	likely_pathogenic	0.6916	pathogenic	-0.136	Destabilizing	0.927	D	0.516	neutral	None	None	None	None	I
N/C	0.8542	likely_pathogenic	0.8801	pathogenic	-0.147	Destabilizing	1.0	D	0.599	neutral	None	None	None	None	I
N/D	0.4236	ambiguous	0.5863	pathogenic	-0.185	Destabilizing	0.979	D	0.39	neutral	N	0.489395234	None	None	I
N/E	0.8191	likely_pathogenic	0.9071	pathogenic	-0.258	Destabilizing	0.969	D	0.385	neutral	None	None	None	None	I
N/F	0.9267	likely_pathogenic	0.9445	pathogenic	-0.81	Destabilizing	0.999	D	0.585	neutral	None	None	None	None	I
N/G	0.4255	ambiguous	0.5191	ambiguous	-0.172	Destabilizing	0.013	N	0.228	neutral	None	None	None	None	I
N/H	0.3674	ambiguous	0.4953	ambiguous	-0.175	Destabilizing	0.998	D	0.458	neutral	N	0.48419418	None	None	I
N/I	0.7116	likely_pathogenic	0.7776	pathogenic	-0.135	Destabilizing	0.998	D	0.581	neutral	N	0.461274251	None	None	I
N/K	0.7368	likely_pathogenic	0.8918	pathogenic	-0.153	Destabilizing	0.238	N	0.227	neutral	N	0.494493149	None	None	I
N/L	0.6603	likely_pathogenic	0.7329	pathogenic	-0.135	Destabilizing	0.984	D	0.554	neutral	None	None	None	None	I
N/M	0.7448	likely_pathogenic	0.8161	pathogenic	-0.167	Destabilizing	1.0	D	0.576	neutral	None	None	None	None	I
N/P	0.8222	likely_pathogenic	0.8484	pathogenic	-0.118	Destabilizing	0.999	D	0.565	neutral	None	None	None	None	I
N/Q	0.6632	likely_pathogenic	0.793	pathogenic	-0.411	Destabilizing	0.991	D	0.431	neutral	None	None	None	None	I
N/R	0.8041	likely_pathogenic	0.9013	pathogenic	-0.064	Destabilizing	0.939	D	0.423	neutral	None	None	None	None	I
N/S	0.1269	likely_benign	0.1639	benign	-0.225	Destabilizing	0.906	D	0.408	neutral	N	0.466649041	None	None	I
N/T	0.3705	ambiguous	0.4643	ambiguous	-0.217	Destabilizing	0.979	D	0.369	neutral	N	0.469328123	None	None	I
N/V	0.6851	likely_pathogenic	0.7527	pathogenic	-0.118	Destabilizing	0.995	D	0.564	neutral	None	None	None	None	I
N/W	0.9754	likely_pathogenic	0.981	pathogenic	-1.004	Destabilizing	1.0	D	0.633	neutral	None	None	None	None	I
N/Y	0.6172	likely_pathogenic	0.6916	pathogenic	-0.683	Destabilizing	0.998	D	0.577	neutral	N	0.473835125	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.