TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35325	106198;106199;106200	chr2:178530642;178530641;178530640	chr2:179395369;179395368;179395367
N2AB	33684	101275;101276;101277	chr2:178530642;178530641;178530640	chr2:179395369;179395368;179395367
N2A	32757	98494;98495;98496	chr2:178530642;178530641;178530640	chr2:179395369;179395368;179395367
N2B	26260	79003;79004;79005	chr2:178530642;178530641;178530640	chr2:179395369;179395368;179395367
Novex-1	26385	79378;79379;79380	chr2:178530642;178530641;178530640	chr2:179395369;179395368;179395367
Novex-2	26452	79579;79580;79581	chr2:178530642;178530641;178530640	chr2:179395369;179395368;179395367
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-165
• Domain position: 40
• Structural Position: 56
• Q(SASA): 0.4783
• 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	None	None	0.089	N	0.547	0.266	0.321672782286	gnomAD-4.0.0	6.84134E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99391E-07	0	0
K/Q	None	None	0.407	N	0.6	0.225	0.32053947749	gnomAD-4.0.0	6.84134E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99391E-07	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	0.4336	ambiguous	0.3728	ambiguous	-0.366	Destabilizing	0.206	N	0.57	neutral	None	None	None	None	N
K/C	0.7798	likely_pathogenic	0.7385	pathogenic	-0.541	Destabilizing	0.955	D	0.659	neutral	None	None	None	None	N
K/D	0.7955	likely_pathogenic	0.731	pathogenic	0.065	Stabilizing	0.476	N	0.631	neutral	None	None	None	None	N
K/E	0.2531	likely_benign	0.2158	benign	0.174	Stabilizing	0.089	N	0.547	neutral	N	0.425025215	None	None	N
K/F	0.8091	likely_pathogenic	0.7651	pathogenic	-0.111	Destabilizing	0.874	D	0.651	neutral	None	None	None	None	N
K/G	0.6792	likely_pathogenic	0.6031	pathogenic	-0.685	Destabilizing	0.476	N	0.527	neutral	None	None	None	None	N
K/H	0.4724	ambiguous	0.4122	ambiguous	-0.733	Destabilizing	0.874	D	0.621	neutral	None	None	None	None	N
K/I	0.295	likely_benign	0.2622	benign	0.443	Stabilizing	0.582	D	0.671	neutral	N	0.474128671	None	None	N
K/L	0.3289	likely_benign	0.2891	benign	0.443	Stabilizing	0.476	N	0.527	neutral	None	None	None	None	N
K/M	0.2091	likely_benign	0.1861	benign	-0.01	Destabilizing	0.955	D	0.616	neutral	None	None	None	None	N
K/N	0.5127	ambiguous	0.4381	ambiguous	-0.331	Destabilizing	0.407	N	0.593	neutral	N	0.507201094	None	None	N
K/P	0.5927	likely_pathogenic	0.5708	pathogenic	0.202	Stabilizing	0.648	D	0.627	neutral	None	None	None	None	N
K/Q	0.1703	likely_benign	0.1488	benign	-0.317	Destabilizing	0.407	N	0.6	neutral	N	0.477147546	None	None	N
K/R	0.1113	likely_benign	0.1029	benign	-0.278	Destabilizing	0.001	N	0.253	neutral	N	0.465815832	None	None	N
K/S	0.5972	likely_pathogenic	0.5134	ambiguous	-0.895	Destabilizing	0.206	N	0.579	neutral	None	None	None	None	N
K/T	0.2542	likely_benign	0.2175	benign	-0.591	Destabilizing	0.407	N	0.585	neutral	N	0.501640559	None	None	N
K/V	0.331	likely_benign	0.294	benign	0.202	Stabilizing	0.476	N	0.619	neutral	None	None	None	None	N
K/W	0.8552	likely_pathogenic	0.8219	pathogenic	-0.081	Destabilizing	0.955	D	0.673	neutral	None	None	None	None	N
K/Y	0.6779	likely_pathogenic	0.6201	pathogenic	0.212	Stabilizing	0.648	D	0.619	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.