TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31108	93547;93548;93549	chr2:178548304;178548303;178548302	chr2:179413031;179413030;179413029
N2AB	29467	88624;88625;88626	chr2:178548304;178548303;178548302	chr2:179413031;179413030;179413029
N2A	28540	85843;85844;85845	chr2:178548304;178548303;178548302	chr2:179413031;179413030;179413029
N2B	22043	66352;66353;66354	chr2:178548304;178548303;178548302	chr2:179413031;179413030;179413029
Novex-1	22168	66727;66728;66729	chr2:178548304;178548303;178548302	chr2:179413031;179413030;179413029
Novex-2	22235	66928;66929;66930	chr2:178548304;178548303;178548302	chr2:179413031;179413030;179413029
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-114
• Domain position: 93
• Structural Position: 127
• Q(SASA): 0.1145
• 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
I/N	None	None	0.177	N	0.735	0.327	0.707919410837	gnomAD-4.0.0	6.84176E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99441E-07	0	0
I/S	None	None	0.03	N	0.547	0.305	0.71193717946	gnomAD-4.0.0	2.05253E-06	None	None	None	None	N	None	2.98757E-05	0	None	0	0	None	0	0	1.79888E-06	0	0
I/T	rs373732722	-2.249	0.001	N	0.281	0.256	None	gnomAD-2.1.1	1.08672E-04	None	None	None	None	N	None	0	1.15902E-04	None	0	5.57E-05	None	2.28758E-04	None	5.57258E-04	2.67E-05	0
I/T	rs373732722	-2.249	0.001	N	0.281	0.256	None	gnomAD-3.1.2	6.57E-05	None	None	None	None	N	None	0	1.3101E-04	0	0	1.92678E-04	None	1.88182E-04	0	4.41E-05	4.1511E-04	0
I/T	rs373732722	-2.249	0.001	N	0.281	0.256	None	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	0	0	None	None	None	1E-03	None
I/T	rs373732722	-2.249	0.001	N	0.281	0.256	None	gnomAD-4.0.0	6.19626E-05	None	None	None	None	N	None	3.99787E-05	1.49985E-04	None	0	2.22836E-05	None	3.59252E-04	0	2.71232E-05	2.74508E-04	1.12032E-04
I/V	rs727504787	-1.009	None	N	0.133	0.048	0.191931220699	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	5.8E-05	None	0	0	None	0	None	0	0	0
I/V	rs727504787	-1.009	None	N	0.133	0.048	0.191931220699	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	1.47E-05	0	0
I/V	rs727504787	-1.009	None	N	0.133	0.048	0.191931220699	gnomAD-4.0.0	1.05345E-05	None	None	None	None	N	None	1.33494E-05	3.33367E-05	None	0	0	None	0	0	9.32352E-06	0	4.80323E-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
I/A	0.2466	likely_benign	0.2165	benign	-1.95	Destabilizing	0.016	N	0.431	neutral	None	None	None	None	N
I/C	0.6606	likely_pathogenic	0.6196	pathogenic	-1.27	Destabilizing	0.685	D	0.52	neutral	None	None	None	None	N
I/D	0.947	likely_pathogenic	0.9105	pathogenic	-1.768	Destabilizing	0.221	N	0.713	prob.delet.	None	None	None	None	N
I/E	0.8494	likely_pathogenic	0.767	pathogenic	-1.586	Destabilizing	0.221	N	0.7	prob.delet.	None	None	None	None	N
I/F	0.2259	likely_benign	0.1713	benign	-1.16	Destabilizing	0.097	N	0.465	neutral	N	0.488531079	None	None	N
I/G	0.7634	likely_pathogenic	0.7169	pathogenic	-2.396	Highly Destabilizing	0.221	N	0.693	prob.delet.	None	None	None	None	N
I/H	0.7686	likely_pathogenic	0.6723	pathogenic	-1.501	Destabilizing	0.869	D	0.729	deleterious	None	None	None	None	N
I/K	0.7217	likely_pathogenic	0.5982	pathogenic	-1.342	Destabilizing	0.221	N	0.693	prob.delet.	None	None	None	None	N
I/L	0.1095	likely_benign	0.09	benign	-0.695	Destabilizing	None	N	0.176	neutral	N	0.462816274	None	None	N
I/M	0.0974	likely_benign	0.0803	benign	-0.721	Destabilizing	0.002	N	0.377	neutral	N	0.495367934	None	None	N
I/N	0.7172	likely_pathogenic	0.6069	pathogenic	-1.637	Destabilizing	0.177	N	0.735	deleterious	N	0.506888824	None	None	N
I/P	0.9578	likely_pathogenic	0.941	pathogenic	-1.092	Destabilizing	0.366	N	0.735	deleterious	None	None	None	None	N
I/Q	0.6999	likely_pathogenic	0.588	pathogenic	-1.54	Destabilizing	0.221	N	0.741	deleterious	None	None	None	None	N
I/R	0.6231	likely_pathogenic	0.4812	ambiguous	-1.072	Destabilizing	0.221	N	0.735	deleterious	None	None	None	None	N
I/S	0.4843	ambiguous	0.3854	ambiguous	-2.297	Highly Destabilizing	0.03	N	0.547	neutral	N	0.505621376	None	None	N
I/T	0.1877	likely_benign	0.1638	benign	-1.965	Destabilizing	0.001	N	0.281	neutral	N	0.475574477	None	None	N
I/V	0.0521	likely_benign	0.0531	benign	-1.092	Destabilizing	None	N	0.133	neutral	N	0.400939555	None	None	N
I/W	0.8772	likely_pathogenic	0.8114	pathogenic	-1.335	Destabilizing	0.869	D	0.753	deleterious	None	None	None	None	N
I/Y	0.7265	likely_pathogenic	0.6143	pathogenic	-1.05	Destabilizing	0.366	N	0.535	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.