Submissions for variant NM_001358530.2(MOCS1):c.1064T>C (p.Ile355Thr)

gnomAD frequency: 0.00159  dbSNP: rs143912353

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000642134	SCV000763787	likely benign	Sulfite oxidase deficiency due to molybdenum cofactor deficiency type A	2024-01-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000642134	SCV001316757	uncertain significance	Sulfite oxidase deficiency due to molybdenum cofactor deficiency type A	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
CeGaT Center for Human Genetics Tuebingen	RCV003222073	SCV003917058	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	MOCS1: BS1
Mayo Clinic Laboratories, Mayo Clinic	RCV003222073	SCV004227234	uncertain significance	not provided	2023-05-16	criteria provided, single submitter	clinical testing	BS1, PP3
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003994058	SCV004812955	likely benign	not specified	2024-02-12	criteria provided, single submitter	clinical testing	Variant summary: MOCS1 c.1064T>C (p.Ile355Thr) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0018 in 1613824 control chromosomes in the gnomAD database, including 3 homozygotes. c.1064T>C has been reported in the literature in one individual affected with Molybdenum Cofactor Deficiency (Macaya_2005), as well as in one individual affected with Epilepsy (Gorukmez_2023). These reports do not provide unequivocal conclusions about association of the variant with Sulfite Oxidase Deficiency Due To Molybdenum Cofactor Deficiency Type A. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 36964972, 36296488, 16429380, 21031595). ClinVar contains an entry for this variant (Variation ID: 534543). Based on the evidence outlined above, the variant was classified as likely benign.
GenomeConnect - Brain Gene Registry	RCV003222073	SCV004801646	not provided	not provided		no assertion provided	phenotyping only	Variant classified as Uncertain significance and reported on 06-25-2021 by Invitae. Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect does not attempt to reinterpret the variant. The IDDRC-CTSA National Brain Gene Registry (BGR) is a study funded by the U.S. National Center for Advancing Translational Sciences (NCATS) and includes 13 Intellectual and Developmental Disability Research Center (IDDRC) institutions. The study is led by Principal Investigator Dr. Philip Payne from Washington University. The BGR is a data commons of gene variants paired with subject clinical information. This database helps scientists learn more about genetic changes and their impact on the brain and behavior. Participation in the Brain Gene Registry requires participation in GenomeConnect. More information about the Brain Gene Registry can be found on the study website - https://braingeneregistry.wustl.edu/.