TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17641	53146;53147;53148	chr2:178607866;178607865;178607864	chr2:179472593;179472592;179472591
N2AB	16000	48223;48224;48225	chr2:178607866;178607865;178607864	chr2:179472593;179472592;179472591
N2A	15073	45442;45443;45444	chr2:178607866;178607865;178607864	chr2:179472593;179472592;179472591
N2B	8576	25951;25952;25953	chr2:178607866;178607865;178607864	chr2:179472593;179472592;179472591
Novex-1	8701	26326;26327;26328	chr2:178607866;178607865;178607864	chr2:179472593;179472592;179472591
Novex-2	8768	26527;26528;26529	chr2:178607866;178607865;178607864	chr2:179472593;179472592;179472591
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: Fn3-16
• Domain position: 73
• Structural Position: 105
• Q(SASA): 0.2572
• 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	rs1454839951	None	0.101	N	0.523	0.186	0.180583059064	gnomAD-4.0.0	1.59271E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8611E-06	0	0
K/R	rs747537364	-1.288	0.001	N	0.235	0.087	0.221734844693	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	6.47E-05	0	None	0	0	None	0	None	4.64E-05	8.89E-06	0
K/R	rs747537364	-1.288	0.001	N	0.235	0.087	0.221734844693	gnomAD-4.0.0	4.77817E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.7223E-06	0	3.02773E-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	0.5688	likely_pathogenic	0.5642	pathogenic	-1.412	Destabilizing	0.228	N	0.52	neutral	None	None	None	None	N
K/C	0.6049	likely_pathogenic	0.5803	pathogenic	-1.457	Destabilizing	0.983	D	0.678	prob.neutral	None	None	None	None	N
K/D	0.8838	likely_pathogenic	0.8756	pathogenic	-1.898	Destabilizing	0.418	N	0.579	neutral	None	None	None	None	N
K/E	0.3692	ambiguous	0.3703	ambiguous	-1.617	Destabilizing	0.101	N	0.523	neutral	N	0.360845159	None	None	N
K/F	0.7046	likely_pathogenic	0.6635	pathogenic	-0.557	Destabilizing	0.716	D	0.664	neutral	None	None	None	None	N
K/G	0.7739	likely_pathogenic	0.7491	pathogenic	-1.878	Destabilizing	0.418	N	0.59	neutral	None	None	None	None	N
K/H	0.3057	likely_benign	0.2897	benign	-2.009	Highly Destabilizing	0.836	D	0.607	neutral	None	None	None	None	N
K/I	0.2295	likely_benign	0.2483	benign	-0.096	Destabilizing	0.007	N	0.629	neutral	N	0.422243121	None	None	N
K/L	0.2636	likely_benign	0.2795	benign	-0.096	Destabilizing	0.002	N	0.565	neutral	None	None	None	None	N
K/M	0.2043	likely_benign	0.2092	benign	-0.476	Destabilizing	0.716	D	0.601	neutral	None	None	None	None	N
K/N	0.6178	likely_pathogenic	0.5989	pathogenic	-1.84	Destabilizing	0.351	N	0.533	neutral	N	0.416373154	None	None	N
K/P	0.9861	likely_pathogenic	0.9835	pathogenic	-0.514	Destabilizing	0.94	D	0.611	neutral	None	None	None	None	N
K/Q	0.1694	likely_benign	0.1651	benign	-1.466	Destabilizing	0.021	N	0.427	neutral	N	0.390592062	None	None	N
K/R	0.083	likely_benign	0.0791	benign	-1.327	Destabilizing	0.001	N	0.235	neutral	N	0.421376329	None	None	N
K/S	0.6162	likely_pathogenic	0.5938	pathogenic	-2.303	Highly Destabilizing	0.418	N	0.537	neutral	None	None	None	None	N
K/T	0.2497	likely_benign	0.248	benign	-1.784	Destabilizing	0.351	N	0.565	neutral	N	0.418661311	None	None	N
K/V	0.2504	likely_benign	0.2672	benign	-0.514	Destabilizing	0.129	N	0.58	neutral	None	None	None	None	N
K/W	0.7276	likely_pathogenic	0.6742	pathogenic	-0.707	Destabilizing	0.983	D	0.709	prob.delet.	None	None	None	None	N
K/Y	0.5628	ambiguous	0.5295	ambiguous	-0.355	Destabilizing	0.94	D	0.653	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.