Submissions for variant NM_005548.3(KARS1):c.433T>C (p.Tyr145His)

gnomAD frequency: 0.00003  dbSNP: rs397514745

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center of Genomic medicine, Geneva, University Hospital of Geneva	RCV000627042	SCV000747747	pathogenic	Nonsyndromic genetic hearing loss	2017-11-20	criteria provided, single submitter	clinical testing	This homozygous variant was identified in a female patient with non-syndromic and progressive deafness, due to bilateral vestibulo-cochlear dysfunction. One of her two brothers who is also deaf also harbours this variant in a homozygous state.
3billion, Medical Genetics	RCV001807772	SCV002058683	uncertain significance	Leukoencephalopathy, progressive, infantile-onset, with or without deafness	2022-01-03	criteria provided, single submitter	clinical testing	Same nucleotide change resulting in same amino acid change has been previously reported to be associated with KARS1 related disorder (ClinVar ID: VCV000060752, PS1_P). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000028, PM2_M). A missense variant is a common mechanism associated with Leukoencephalopathy (PP2_P).Therefore, this variant is classified as uncertain significance according to the recommendation of ACMG/AMP guideline.
OMIM	RCV000054525	SCV000083003	pathogenic	Autosomal recessive nonsyndromic hearing loss 89	2013-07-11	no assertion criteria provided	literature only
Department of Molecular and Human Genetics, Baylor College of Medicine	RCV000054525	SCV000249614	pathogenic	Autosomal recessive nonsyndromic hearing loss 89	2014-01-17	no assertion criteria provided	research