TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14867	44824;44825;44826	chr2:178624681;178624680;178624679	chr2:179489408;179489407;179489406
N2AB	13226	39901;39902;39903	chr2:178624681;178624680;178624679	chr2:179489408;179489407;179489406
N2A	12299	37120;37121;37122	chr2:178624681;178624680;178624679	chr2:179489408;179489407;179489406
N2B	5802	17629;17630;17631	chr2:178624681;178624680;178624679	chr2:179489408;179489407;179489406
Novex-1	5927	18004;18005;18006	chr2:178624681;178624680;178624679	chr2:179489408;179489407;179489406
Novex-2	5994	18205;18206;18207	chr2:178624681;178624680;178624679	chr2:179489408;179489407;179489406
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-100
• Domain position: 15
• Structural Position: 24
• Q(SASA): 0.5254
• 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
G/A	rs1317888739	-0.244	0.027	D	0.373	0.419	0.393623145366	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
G/A	rs1317888739	-0.244	0.027	D	0.373	0.419	0.393623145366	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
G/A	rs1317888739	-0.244	0.027	D	0.373	0.419	0.393623145366	gnomAD-4.0.0	6.58207E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47232E-05	0	0
G/E	rs1317888739	None	None	D	0.241	0.355	0.535679682109	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-06	0	0
G/R	rs144848584	-0.316	0.062	D	0.522	0.426	0.74873181118	gnomAD-2.1.1	1.41208E-04	None	None	None	None	N	None	0	0	None	0	1.91205E-03	None	0	None	0	0	1.66445E-04
G/R	rs144848584	-0.316	0.062	D	0.522	0.426	0.74873181118	gnomAD-3.1.2	7.24E-05	None	None	None	None	N	None	0	0	0	0	2.13841E-03	None	0	0	0	0	0
G/R	rs144848584	-0.316	0.062	D	0.522	0.426	0.74873181118	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	1E-03	0	None	None	None	0	None
G/R	rs144848584	-0.316	0.062	D	0.522	0.426	0.74873181118	gnomAD-4.0.0	1.28999E-04	None	None	None	None	N	None	0	0	None	0	4.56826E-03	None	0	0	8.48151E-07	0	4.80831E-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
G/A	0.1637	likely_benign	0.1482	benign	-0.358	Destabilizing	0.027	N	0.373	neutral	D	0.586968316	None	None	N
G/C	0.4353	ambiguous	0.4143	ambiguous	-0.868	Destabilizing	0.935	D	0.629	neutral	None	None	None	None	N
G/D	0.2123	likely_benign	0.1994	benign	-0.681	Destabilizing	0.016	N	0.43	neutral	None	None	None	None	N
G/E	0.1025	likely_benign	0.0885	benign	-0.851	Destabilizing	None	N	0.241	neutral	D	0.543324697	None	None	N
G/F	0.595	likely_pathogenic	0.6015	pathogenic	-1.16	Destabilizing	0.791	D	0.639	neutral	None	None	None	None	N
G/H	0.399	ambiguous	0.3893	ambiguous	-0.585	Destabilizing	0.555	D	0.609	neutral	None	None	None	None	N
G/I	0.4853	ambiguous	0.41	ambiguous	-0.513	Destabilizing	0.555	D	0.628	neutral	None	None	None	None	N
G/K	0.2663	likely_benign	0.2322	benign	-0.746	Destabilizing	0.035	N	0.47	neutral	None	None	None	None	N
G/L	0.4189	ambiguous	0.4129	ambiguous	-0.513	Destabilizing	0.149	N	0.582	neutral	None	None	None	None	N
G/M	0.4233	ambiguous	0.396	ambiguous	-0.395	Destabilizing	0.935	D	0.629	neutral	None	None	None	None	N
G/N	0.2576	likely_benign	0.2526	benign	-0.414	Destabilizing	0.149	N	0.341	neutral	None	None	None	None	N
G/P	0.9341	likely_pathogenic	0.9233	pathogenic	-0.429	Destabilizing	0.262	N	0.572	neutral	None	None	None	None	N
G/Q	0.2286	likely_benign	0.2145	benign	-0.746	Destabilizing	0.081	N	0.474	neutral	None	None	None	None	N
G/R	0.2415	likely_benign	0.2076	benign	-0.277	Destabilizing	0.062	N	0.522	neutral	D	0.540260232	None	None	N
G/S	0.1727	likely_benign	0.161	benign	-0.558	Destabilizing	0.035	N	0.384	neutral	None	None	None	None	N
G/T	0.2046	likely_benign	0.1864	benign	-0.663	Destabilizing	0.149	N	0.503	neutral	None	None	None	None	N
G/V	0.3494	ambiguous	0.2798	benign	-0.429	Destabilizing	0.117	N	0.551	neutral	D	0.686391947	None	None	N
G/W	0.4883	ambiguous	0.4324	ambiguous	-1.28	Destabilizing	0.935	D	0.607	neutral	None	None	None	None	N
G/Y	0.4667	ambiguous	0.447	ambiguous	-0.929	Destabilizing	0.791	D	0.634	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.