TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16126	48601;48602;48603	chr2:178615725;178615724;178615723	chr2:179480452;179480451;179480450
N2AB	14485	43678;43679;43680	chr2:178615725;178615724;178615723	chr2:179480452;179480451;179480450
N2A	13558	40897;40898;40899	chr2:178615725;178615724;178615723	chr2:179480452;179480451;179480450
N2B	7061	21406;21407;21408	chr2:178615725;178615724;178615723	chr2:179480452;179480451;179480450
Novex-1	7186	21781;21782;21783	chr2:178615725;178615724;178615723	chr2:179480452;179480451;179480450
Novex-2	7253	21982;21983;21984	chr2:178615725;178615724;178615723	chr2:179480452;179480451;179480450
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Fn3-4
• Domain position: 72
• Structural Position: 105
• Q(SASA): 0.1496
• 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
L/S	rs764312225	-2.565	0.638	N	0.685	0.403	0.785186314975	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
L/S	rs764312225	-2.565	0.638	N	0.685	0.403	0.785186314975	gnomAD-4.0.0	3.18862E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72908E-06	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
L/A	0.359	ambiguous	0.4375	ambiguous	-2.38	Highly Destabilizing	0.25	N	0.613	neutral	None	None	None	None	N
L/C	0.434	ambiguous	0.4911	ambiguous	-1.237	Destabilizing	0.947	D	0.701	prob.neutral	None	None	None	None	N
L/D	0.8757	likely_pathogenic	0.9082	pathogenic	-2.918	Highly Destabilizing	0.826	D	0.78	deleterious	None	None	None	None	N
L/E	0.5676	likely_pathogenic	0.6287	pathogenic	-2.633	Highly Destabilizing	0.826	D	0.765	deleterious	None	None	None	None	N
L/F	0.1262	likely_benign	0.1447	benign	-1.364	Destabilizing	0.638	D	0.659	neutral	N	0.465580704	None	None	N
L/G	0.7513	likely_pathogenic	0.7905	pathogenic	-2.938	Highly Destabilizing	0.826	D	0.733	prob.delet.	None	None	None	None	N
L/H	0.26	likely_benign	0.31	benign	-2.624	Highly Destabilizing	0.982	D	0.757	deleterious	None	None	None	None	N
L/I	0.0915	likely_benign	0.0987	benign	-0.721	Destabilizing	0.002	N	0.477	neutral	N	0.459820282	None	None	N
L/K	0.4785	ambiguous	0.5116	ambiguous	-1.639	Destabilizing	0.826	D	0.687	prob.neutral	None	None	None	None	N
L/M	0.1166	likely_benign	0.1342	benign	-0.69	Destabilizing	0.7	D	0.687	prob.neutral	None	None	None	None	N
L/N	0.5759	likely_pathogenic	0.6151	pathogenic	-2.186	Highly Destabilizing	0.935	D	0.777	deleterious	None	None	None	None	N
L/P	0.9751	likely_pathogenic	0.9798	pathogenic	-1.262	Destabilizing	0.935	D	0.781	deleterious	None	None	None	None	N
L/Q	0.2046	likely_benign	0.2419	benign	-1.91	Destabilizing	0.935	D	0.73	prob.delet.	None	None	None	None	N
L/R	0.3025	likely_benign	0.3429	ambiguous	-1.632	Destabilizing	0.826	D	0.729	prob.delet.	None	None	None	None	N
L/S	0.3868	ambiguous	0.462	ambiguous	-2.737	Highly Destabilizing	0.638	D	0.685	prob.neutral	N	0.470577966	None	None	N
L/T	0.301	likely_benign	0.356	ambiguous	-2.311	Highly Destabilizing	0.539	D	0.663	neutral	None	None	None	None	N
L/V	0.0938	likely_benign	0.1092	benign	-1.262	Destabilizing	0.002	N	0.338	neutral	N	0.45133411	None	None	N
L/W	0.3174	likely_benign	0.3478	ambiguous	-1.836	Destabilizing	0.982	D	0.677	prob.neutral	None	None	None	None	N
L/Y	0.3155	likely_benign	0.3444	ambiguous	-1.528	Destabilizing	0.826	D	0.703	prob.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.