TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14396	43411;43412;43413	chr2:178632945;178632944;178632943	chr2:179497672;179497671;179497670
N2AB	12755	38488;38489;38490	chr2:178632945;178632944;178632943	chr2:179497672;179497671;179497670
N2A	11828	35707;35708;35709	chr2:178632945;178632944;178632943	chr2:179497672;179497671;179497670
N2B	5331	16216;16217;16218	chr2:178632945;178632944;178632943	chr2:179497672;179497671;179497670
Novex-1	5456	16591;16592;16593	chr2:178632945;178632944;178632943	chr2:179497672;179497671;179497670
Novex-2	5523	16792;16793;16794	chr2:178632945;178632944;178632943	chr2:179497672;179497671;179497670
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-94
• Domain position: 78
• Structural Position: 163
• Q(SASA): 0.3059
• 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/T	None	None	0.999	N	0.821	0.459	0.246215685461	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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	0.6415	likely_pathogenic	0.5433	ambiguous	-0.181	Destabilizing	0.998	D	0.746	deleterious	None	None	None	None	N
K/C	0.9087	likely_pathogenic	0.8782	pathogenic	-0.196	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
K/D	0.9017	likely_pathogenic	0.8162	pathogenic	0.215	Stabilizing	0.999	D	0.831	deleterious	None	None	None	None	N
K/E	0.4068	ambiguous	0.2932	benign	0.247	Stabilizing	0.997	D	0.656	prob.neutral	N	0.445227066	None	None	N
K/F	0.9275	likely_pathogenic	0.8719	pathogenic	-0.258	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
K/G	0.806	likely_pathogenic	0.7287	pathogenic	-0.439	Destabilizing	0.999	D	0.694	prob.delet.	None	None	None	None	N
K/H	0.5573	ambiguous	0.4566	ambiguous	-0.819	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
K/I	0.5969	likely_pathogenic	0.491	ambiguous	0.435	Stabilizing	0.999	D	0.745	deleterious	D	0.559753304	None	None	N
K/L	0.685	likely_pathogenic	0.5894	pathogenic	0.435	Stabilizing	0.999	D	0.694	prob.delet.	None	None	None	None	N
K/M	0.4896	ambiguous	0.4088	ambiguous	0.351	Stabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
K/N	0.7428	likely_pathogenic	0.6074	pathogenic	0.179	Stabilizing	0.999	D	0.775	deleterious	N	0.50160239	None	None	N
K/P	0.9648	likely_pathogenic	0.9432	pathogenic	0.259	Stabilizing	0.999	D	0.827	deleterious	None	None	None	None	N
K/Q	0.2387	likely_benign	0.196	benign	-0.006	Destabilizing	0.999	D	0.757	deleterious	N	0.432887648	None	None	N
K/R	0.1172	likely_benign	0.1112	benign	-0.141	Destabilizing	0.997	D	0.601	neutral	N	0.435744959	None	None	N
K/S	0.6591	likely_pathogenic	0.5415	ambiguous	-0.422	Destabilizing	0.998	D	0.667	prob.neutral	None	None	None	None	N
K/T	0.3107	likely_benign	0.2403	benign	-0.218	Destabilizing	0.999	D	0.821	deleterious	N	0.425181517	None	None	N
K/V	0.5206	ambiguous	0.4322	ambiguous	0.259	Stabilizing	0.999	D	0.753	deleterious	None	None	None	None	N
K/W	0.9411	likely_pathogenic	0.9056	pathogenic	-0.19	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
K/Y	0.8744	likely_pathogenic	0.8065	pathogenic	0.146	Stabilizing	1.0	D	0.757	deleterious	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.