Submissions for variant NM_004006.3(DMD):c.9649T>C (p.Tyr3217His)

gnomAD frequency: 0.00003  dbSNP: rs766981643

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000704664	SCV000833620	uncertain significance	Duchenne muscular dystrophy	2023-12-20	criteria provided, single submitter	clinical testing	This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 3217 of the DMD protein (p.Tyr3217His). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with DMD-related conditions. ClinVar contains an entry for this variant (Variation ID: 580971). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Revvity Omics, Revvity	RCV001702712	SCV003834769	uncertain significance	not provided	2020-06-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004993973	SCV005566463	uncertain significance	Cardiovascular phenotype	2024-11-09	criteria provided, single submitter	clinical testing	The p.Y3217H variant (also known as c.9649T>C), located in coding exon 66 of the DMD gene, results from a T to C substitution at nucleotide position 9649. The amino acid change results in tyrosine to histidine at codon 3217, an amino acid with similar properties. Based on data from gnomAD, the C allele has an overall frequency of <0.01% (3/200144) total alleles studied, with 1 hemizygote(s) observed. The highest observed frequency was <0.01% (1/14659) of East Asian alleles. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001702712	SCV001931615	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001702712	SCV001966174	uncertain significance	not provided		no assertion criteria provided	clinical testing
Natera, Inc.	RCV001830557	SCV002077651	uncertain significance	Becker muscular dystrophy; Duchenne muscular dystrophy; Cardiomyopathy; Dystrophin deficiency	2019-01-18	no assertion criteria provided	clinical testing