TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18947	57064;57065;57066	chr2:178598871;178598870;178598869	chr2:179463598;179463597;179463596
N2AB	17306	52141;52142;52143	chr2:178598871;178598870;178598869	chr2:179463598;179463597;179463596
N2A	16379	49360;49361;49362	chr2:178598871;178598870;178598869	chr2:179463598;179463597;179463596
N2B	9882	29869;29870;29871	chr2:178598871;178598870;178598869	chr2:179463598;179463597;179463596
Novex-1	10007	30244;30245;30246	chr2:178598871;178598870;178598869	chr2:179463598;179463597;179463596
Novex-2	10074	30445;30446;30447	chr2:178598871;178598870;178598869	chr2:179463598;179463597;179463596
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Fn3-25
• Domain position: 64
• Structural Position: 90
• Q(SASA): 0.1243
• 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
S/A	rs1357569723	-0.932	0.625	N	0.558	0.2	0.19670166235	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

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
S/A	0.1942	likely_benign	0.1507	benign	-0.685	Destabilizing	0.625	D	0.558	neutral	N	0.510248894	None	None	N
S/C	0.245	likely_benign	0.2035	benign	-0.452	Destabilizing	0.997	D	0.595	neutral	N	0.482390057	None	None	N
S/D	0.9008	likely_pathogenic	0.8062	pathogenic	0.126	Stabilizing	0.728	D	0.557	neutral	None	None	None	None	N
S/E	0.9164	likely_pathogenic	0.8323	pathogenic	0.151	Stabilizing	0.842	D	0.57	neutral	None	None	None	None	N
S/F	0.6939	likely_pathogenic	0.5369	ambiguous	-1.003	Destabilizing	0.028	N	0.511	neutral	N	0.517849657	None	None	N
S/G	0.272	likely_benign	0.2112	benign	-0.928	Destabilizing	0.688	D	0.529	neutral	None	None	None	None	N
S/H	0.7775	likely_pathogenic	0.6378	pathogenic	-1.236	Destabilizing	0.974	D	0.596	neutral	None	None	None	None	N
S/I	0.6581	likely_pathogenic	0.4849	ambiguous	-0.142	Destabilizing	0.904	D	0.595	neutral	None	None	None	None	N
S/K	0.9754	likely_pathogenic	0.9391	pathogenic	-0.339	Destabilizing	0.842	D	0.569	neutral	None	None	None	None	N
S/L	0.4826	ambiguous	0.3345	benign	-0.142	Destabilizing	0.728	D	0.573	neutral	None	None	None	None	N
S/M	0.5606	ambiguous	0.4143	ambiguous	-0.155	Destabilizing	0.993	D	0.589	neutral	None	None	None	None	N
S/N	0.4491	ambiguous	0.3305	benign	-0.438	Destabilizing	0.067	N	0.31	neutral	None	None	None	None	N
S/P	0.9131	likely_pathogenic	0.8644	pathogenic	-0.29	Destabilizing	0.989	D	0.588	neutral	N	0.517849657	None	None	N
S/Q	0.8371	likely_pathogenic	0.7371	pathogenic	-0.456	Destabilizing	0.974	D	0.561	neutral	None	None	None	None	N
S/R	0.9519	likely_pathogenic	0.8998	pathogenic	-0.3	Destabilizing	0.974	D	0.581	neutral	None	None	None	None	N
S/T	0.2037	likely_benign	0.1384	benign	-0.438	Destabilizing	0.801	D	0.563	neutral	N	0.46443646	None	None	N
S/V	0.6037	likely_pathogenic	0.4302	ambiguous	-0.29	Destabilizing	0.842	D	0.569	neutral	None	None	None	None	N
S/W	0.7786	likely_pathogenic	0.666	pathogenic	-1.039	Destabilizing	0.998	D	0.669	neutral	None	None	None	None	N
S/Y	0.6193	likely_pathogenic	0.4621	ambiguous	-0.709	Destabilizing	0.111	N	0.515	neutral	N	0.514521351	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.